In-situ conditioning in mass spectrometer systems

ABSTRACT

In a mass spectrometer or gas chromatograph/mass spectrometer system, a conditioning gas such as, for example, hydrogen is added to condition or clean one or more components or regions of the mass spectrometer such as the ion source. The conditioning gas may be added upstream of the mass spectrometer such as, for example, into a sample inlet or a chromatographic column, or may be added directly into the mass spectrometer. The conditioning gas may be added off-line, when the mass spectrometer is not analyzing a sample, or on-line during sample analysis. When added on-line, the conditioning gas may be mixed with a carrier gas such as, for example, helium. In another embodiment, the conditioning gas also serves as the carrier gas through the column; another gas such as, for example, helium may be added to the carrier gas stream.

TECHNICAL FIELD

The present invention relates generally to mass spectrometry, includingmass spectrometry coupled with gas chromatography. More particularly,the invention relates to conditioning a mass spectrometer to improve orrestore its performance.

BACKGROUND

A mass spectrometer (MS) typically includes an ion source for producingcharged species from an introduced sample, a mass analyzer forseparating the charged species according to their mass-to-charge ratios(m/z ratios, or simply “masses”), and an ion detector for counting theseparated species to provide signals from which mass spectra may beproduced. The sample may be introduced into the ion source by varioustechniques. In one example, a gas chromatograph (GC) is interfaced withthe MS such that the sample output from the GC column—containingchromatographically separated sample components—serves as the sampleinput into the ion source. The latter system is often termed a GC/MSsystem.

As an MS continues to be operated over time, invariably some alterationor degradation in the performance of the MS occurs due to the samples,their matrix (e.g., heavy hydrocarbons in petroleum samples,triglycerides in fat samples) and solvents, stationary phase bleed fromthe GC column, or other recalcitrant substances, all of which mayaccumulate over time. Even at the initial operation of the MS, the MSmay not be stabilized or “conditioned” to provide adequate or uniformperformance. In the case of gas chromatography where an electron impact(EI) or chemical ionization (CI) source is typically utilized in the MS,the ion source can be rapidly fouled by the introduced samplecomponents, which results in degraded performance as seen in the analytesignal or spectral characteristics. Another problem, especially withhigh-boiling analytes, is that peak tailing can increase with continueduse in addition to reduced signal response. The degraded performance maybe manifested in many ways but typically the metrics are reduced analytesignal response and high system background noise, the latter beingparticularly troublesome for analyte detection and identification.

These problems require that the MS be cleaned periodically. Generally,the higher the rate of contaminant deposition, the more often the MSmust be cleaned. The common, conventional cleaning solution has been tovent the MS system, remove the critically affected components (e.g., ionsource, ion optics, pre-filter, etc.), treat the removed components tomechanical and/or chemical cleaning followed by other processes (e.g.,muffle or vacuum furnace baking), and then re-install the components inthe MS system. Such conventional ex situ cleaning procedures can bequite complex and lengthy procedures, involving potentially toxicsolvents, expensive equipment, and the time and care of skilledtechnicians. Moreover, the cleaning process only temporarily solves theproblem. After performing an iteration of cleaning and resuming theanalytical operation of the MS, the performance of the MS will start todegrade again, eventually requiring another iteration of cleaning. Inaddition, the conventional cleaning process may fail due to mechanicalissues associated with the reinstallation of components, or because somestep in the procedure was compromised (e.g., a cleaning solvent wascontaminated). Such failures may not be discovered until the MS isreassembled, under vacuum, and at operating conditions. Also, theprocess of venting entrains certain background species, the mostabundant of which is water, which results in additional time beingrequired to eliminate these substances. Water as a contaminant can causea rapid reduction in MS signal response.

Helium is the most commonly employed carrier gas in GC/MS due tohelium's inertness, low mass, high ionization potential, and desirablechromatographic properties. Moreover, spectral reference libraries suchas NIST 08 (National Institute of Standards and Technology) are recordedusing helium as the carrier gas. Helium alone, however, does not possessany inherent cleaning or conditioning properties, and hence its use as acarrier gas cannot ameliorate the need for frequently carrying out theabove-described cleaning procedures. It would thus be desirable toprovide a solution to this problem that prevents the response loss andtailing that occurs when using helium as a carrier gas, and/or reducesor eliminates the need to clean the MS system by the above-describedconventional techniques while still retaining the benefits of usinghelium as a carrier gas.

Hydrogen has also been employed as a carrier gas, but much more rarelythan helium and other carrier gases. A number of significantdisadvantages attend the use of hydrogen as a carrier gas. Hydrogen ishighly combustible. The choice of column dimensions is severely limitedwith hydrogen due to its low viscosity. Much smaller columns arerequired to maintain a positive inlet pressure when the column outlet isan MS. The signal-to-noise ratio of a mass spectrum or chromatogram whenusing hydrogen as the carrier gas is much lower, resulting in detectionlimits that are five to ten times worse than when using helium as thecarrier gas. The use of hydrogen can lead to degradation reactions ofanalytes in the ion source, resulting in a peak tail having a differentcomposition than the apex of the associated peak. This comprises thespectral fidelity, which is an important factor in analyteidentification when employing spectral library searches. Also, thepresence of hydrogen in the sample inlet and the column can result inchemical reactions with analytes that change their structure.

In view of the foregoing, there is an ongoing need in mass spectrometry,including gas chromatography/mass spectrometry, for methods andapparatus for conditioning an MS system. There is also a need formethods and apparatus for in situ conditioning that is carried out atthe MS system, whereby the need for conventional ex situ cleaning iseliminated or at least significantly reduced. There is also a need formethods and apparatus that make effective use of hydrogen and/or othergases in MS systems as an alternative to, or in conjunction with, morecommon gases such as helium.

SUMMARY

To address the foregoing problems, in whole or in part, and/or otherproblems that may have been observed by persons skilled in the art, thepresent disclosure provides methods, processes, systems, apparatus,instruments, and/or devices, as described by way of example inimplementations set forth below.

According to one embodiment, a method for operating a mass spectrometer(MS) system includes introducing a sample and a carrier gas into anionization chamber of the MS system; and flowing a conditioning gas intoa mass spectrometer of the MS system, wherein the conditioning gas inthe mass spectrometer does not substantially change the mass spectralcharacteristics of analytes of the sample, and the conditioning gas isdifferent from the carrier gas.

According to another embodiment, a method for operating a massspectrometer (MS) system includes flowing a conditioning gas into a massspectrometer of the MS system without introducing a sample into the massspectrometer, wherein the mass spectrometer is conditioned by theconditioning gas; and introducing a sample with a carrier gas into theconditioned mass spectrometer and collecting analytical data from thesample, wherein the carrier gas is different from the conditioning gas.

According to another embodiment, a method for operating a massspectrometer (MS) system includes flowing a sample and a carrier gasthrough a column and into an ionization chamber of the MS system; andflowing a conditioning gas into a mass spectrometer of the MS system,wherein the conditioning gas is different from the carrier gas.

According to another embodiment, a method for operating a massspectrometer (MS) system includes operating the MS system in ananalytical mode by flowing a sample and a carrier gas through a columnand into an ionization chamber of the MS system; ceasing operating theMS system in the analytical mode by ceasing the flowing of the sample;and operating the MS system in a conditioning mode to condition one ormore components of the mass spectrometer by flowing a conditioning gasinto the mass spectrometer, wherein the conditioning gas is differentfrom the carrier gas. The conditioning gas may be, for example,hydrogen, argon, ammonia, and/or methane.

According to another embodiment, a method for operating a massspectrometer (MS) system includes flowing a sample and a carrier gasthrough a column and into an ionization chamber of the MS system; whileflowing the sample and the carrier gas, flowing a conditioning gas intoa mass spectrometer of the MS system, wherein the conditioning gas isdifferent from the carrier gas; and ionizing components of the sample inthe ionization chamber. The conditioning gas may be, for example,hydrogen, argon, ammonia, and/or methane.

According to another embodiment, a method for operating a massspectrometer (MS) system includes flowing a sample and a carrier gasthrough a column and into an ionization chamber of the MS system; whileflowing the sample and the carrier gas, flowing an auxiliary gas intothe ionization chamber, wherein the auxiliary gas is different from thecarrier gas; and ionizing components of the sample in the ionizationchamber. The carrier gas may be, for example, hydrogen, argon, ammonia,and/or methane.

According to another embodiment, a method for operating a massspectrometer (MS) system includes flowing a sample and a carrier gasthrough a column and into an ionization chamber of the MS system, thecarrier gas selected from the group consisting of hydrogen, argon,ammonia, and methane; while flowing the sample and the carrier gas,flowing an auxiliary gas into a mass spectrometer of the MS system,wherein the auxiliary gas is different from the carrier gas and isselected from the group consisting of helium, nitrogen, and argon; andionizing components of the sample in the ionization chamber.

According to another embodiment, a mass spectrometer (MS) system,comprising a mass spectrometer and a conditioning gas system isconfigured for performing any of the above methods. The MS system mayinclude a mass spectrometer and a conditioning system. The MS system mayalso include a gas chromatograph.

According to another embodiment, a mass spectrometer (MS) systemincludes a mass spectrometer including a sample interface and anionization chamber communicating with the sample interface; aconditioning gas line configured for fluid communication with aconditioning gas source; a device or apparatus for operating in ananalytical mode, configured for establishing a sample flow path throughthe sample interface and into the ionization chamber; and a device orapparatus for operating in a conditioning mode, configured forestablishing a conditioning gas flow path from the conditioning gassource, through the conditioning gas line and into the massspectrometer.

According to another embodiment, a mass spectrometer (MS) systemincludes a mass spectrometer including a sample interface and anionization chamber communicating with the sample interface; aconditioning gas source; a conditioning gas line configured for fluidcommunication with a conditioning gas source and for directing aconditioning gas toward the mass spectrometer; and a device or apparatusfor regulating respective flows of a carrier gas and the conditioninggas into the mass spectrometer.

According to another embodiment, a mass spectrometer (MS) systemincludes a mass spectrometer including a sample interface and anionization chamber communicating with the sample interface, wherein thesample interface is configured for fluid communication with a carriergas source and the carrier gas source is configured for supplying acarrier gas; an auxiliary gas line configured for fluid communicationwith a auxiliary gas source, wherein the auxiliary gas source isconfigured for supplying an auxiliary gas different from the carriergas, and the auxiliary gas line is configured for adding the auxiliarygas to the carrier gas; and a device or apparatus for regulatingrespective flows of the carrier gas and the auxiliary gas into theionization chamber such that the proportion of the auxiliary gasrelative to the carrier gas flowing into the ionization chamber rangesfrom 0% to less than 100% by volume. The carrier gas may be hydrogen,argon, ammonia, and/or methane.

According to another embodiment, a computer-readable storage medium isprovided that includes instructions for performing any of the abovemethods.

According to another embodiment, a mass spectrometer (MS) system isprovided that includes the computer-readable storage medium.

In some embodiments, the conditioning gas may be or include hydrogen,argon, fluorine, oxygen, ammonia, and/or methane. In some embodiments,the carrier gas may be or include helium, nitrogen or argon. In someembodiments, the conditioning gas is or includes hydrogen and thecarrier gas is or includes helium.

In other embodiments, the carrier gas is hydrogen, and an auxiliary gassuch as, for example, helium, is added to the hydrogen.

Other devices, apparatus, systems, methods, features and advantages ofthe invention will be or will become apparent to one with skill in theart upon examination of the following figures and detailed description.It is intended that all such additional systems, methods, features andadvantages be included within this description, be within the scope ofthe invention, and be protected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be better understood by referring to the followingfigures. The components in the figures are not necessarily to scale,emphasis instead being placed upon illustrating the principles of theinvention. In the figures, like reference numerals designatecorresponding parts throughout the different views.

FIG. 1 is a schematic view of an example of a mass spectrometry (MS)system in accordance with the present disclosure.

FIG. 2 illustrates a mass spectral measurement of a conditioning gas anda carrier gas through an MS system, the ratio of abundances of which maybe utilized to determine the amount of conditioning gas to be providedto the MS system in accordance with the present disclosure.

FIG. 3A illustrates a mass spectrum indicative of heavy fouling of an MSsystem.

FIG. 3B illustrates a mass spectrum generated from the same MS system asin FIG. 3A, but after subjecting the MS system to a conditioning processin accordance with the present disclosure.

FIG. 3C illustrates the same mass spectrum as FIG. 3B, but on anexpanded scale.

FIG. 4A is a Reconstructed Total Ion Chromatogram (RTIC, or TIC) as afunction of time generated from running an MS system without anyconditioning process.

FIG. 4B is another RTIC of the same MS system as in FIG. 4A, but after240 minutes the MS system was treated to an off-line conditioningprocess for two hours using hydrogen as the conditioning agent, inaccordance with the present disclosure.

FIGS. 5A-5E are ion chromatograms as a function of time for theindividual ion masses 55-u, 105-u, 91-u, 215-u and 207-u, respectively;the chromatograms were generated from running an MS system and treatingthe MS system to the conditioning process after about 250 and 270minutes.

FIG. 6A is a reconstructed ion chromatogram for selected ion monitoring(SIM) acquisitions of octafluoronaphthalene in a contaminated MS system.

FIG. 6B is a reconstructed ion chromatogram for SIM acquisitions ofoctafluoronaphthalene in the same MS system as in FIG. 6A, but after theMS system was treated to an off-line conditioning process using hydrogenas the conditioning agent, in accordance with the present disclosure.

FIG. 7 is a schematic view of an example of an MS system configured foron-line conditioning in accordance with the present disclosure.

FIG. 8 is chromatogram obtained from an analysis of a sample of threen-alkane hydrocarbons, n-tetradecane (n-C₁₄), n-pentadecane (n-C₁₅) andn-hexadecane (n-C₁₆), run through the MS system illustrated in FIG. 7.

FIG. 9 is a plot of raw integrator areas for twenty-two consecutive runsof the sample of FIG. 8 without a conditioning gas being added,normalized to the first injection and plotted for the three compounds.

FIG. 10 is a plot of raw integrator areas for twenty-one consecutiveruns of the sample of FIG. 8 with a conditioning gas being added,normalized to the first injection and plotted for the three compounds.

FIG. 11 is a schematic view of another example of an MS systemconfigured for on-line conditioning in accordance with the presentdisclosure.

FIG. 12 is an MS SIM TIC and an FID chromatogram obtained from ananalysis of a sample of eight pollutants run through the MS systemillustrated in FIG. 11.

FIG. 13 is a plot of mass spectrometer-to-flame ionization detector(MS:FID) area ratios for the first five and last five of twentyconsecutive analyses of the sample of FIG. 12, without a conditioninggas being added in accordance with the present disclosure, wherein theratios for each compound are normalized to that of the first injection.

FIG. 14 is a plot of MS:FID area ratios for the first five and last fiveof thirty consecutive analyses of the sample of FIG. 12, with aconditioning gas being added, wherein the ratios for each compound arenormalized to that of the first injection.

FIG. 15 is a schematic view of another example of an MS systemconfigured for on-line conditioning in accordance with the presentdisclosure.

FIG. 16 is an MS SIM TIC and an FID chromatogram obtained from ananalysis of a sample of nine solvent compounds run through the MS systemillustrated in FIG. 15.

FIG. 17 is a plot of mass spectrometer-to-flame ionization detector(MS:FID) area ratios for nine consecutive analyses of the sample of FIG.16 with a conditioning gas added in accordance with the presentdisclosure, followed by eleven consecutive analyses of the samplewithout the conditioning gas being added, wherein the ratios for eachcompound are normalized to that of the first injection made with thehydrogen added.

FIG. 18 shows a typical spectrum of background ion masses observed whenemploying only hydrogen as the carrier gas in a typical GC/MS system.

FIG. 19 is a schematic view of another example of an MS systemconfigured for on-line conditioning in accordance with the presentdisclosure.

FIG. 20 shows two TICs obtained from a chromatographic run of sample oftwenty-eight compounds through the MS system illustrated in FIG. 19,utilizing hydrogen as a carrier gas and helium as a post-columnauxiliary, wherein the upper TIC was shortly after the chromatographicrun was initiated and the lower TIC was acquired after the MS systembecame clean.

DETAILED DESCRIPTION

As used herein, the term “mass spectrometer system” (or “MS system”)refers to a system that includes a mass spectrometer with or without agas chromatograph (GC) being operatively interfaced with the massspectrometer. Thus, for convenience the term “MS system” may alsoencompass (or be used interchangeably with) the term “gaschromatograph/mass spectrometer system” (or “GC/MS system”), dependingon the particular embodiment of interest.

In the context of the present disclosure, the term “analyte” refersgenerally to any sample molecule of interest to a researcher or user ofan MS system—that is, a molecule on which an analysis is desired suchas, for example, a chromatographic or chromatographic/mass spectralanalysis. The term “sample” or “sample matrix” refers to any substanceknown or suspected of containing analytes. The sample may include acombination of analytes and non-analytes. The term “non-analytes” or“non-analytical components” in this context refers to components of thesample for which analysis is not of interest because such components donot have analytical value and/or impair (e.g., interfere with) theanalysis of the desired analytes. Non-analytes may generally be anymolecules not of interest such as contaminants or impurities. Examplesof non-analytes may include, but are not limited to, water, oils,solvents or other media in which the desired analytes may be found, aswell as stationary phase material that has bled from a chromatographiccolumn. The source of non-analytes may be the sample being analyzed atthe time of operating an MS system to acquire analytical data on thesample. Alternatively or additionally, non-analytes may be residualspecies already present in the mass spectrometer prior to operating theMS system to acquire analytical data at a given time, such residualspecies having accumulated as a result prior use(s) of the MS system.

For purposes of the present disclosure, the term “analyte” also refersto compounds that may be analyzed by the MS system for the purpose ofproviding a reference, standard, tuning vehicle, or calibrant.

The present disclosure describes various embodiments entailing theaddition of a conditioning gas (or conditioning agent) to a massspectrometer (MS) system to condition (or re-condition) the MS system insitu so as to improve or restore its performance. Without wishing to bebound by any particular theory at the present time, the conditioning gasmay serve one or more of the following functions: cleaning one or moresurfaces (e.g., walls, plates, electrodes, conduits) of one or morecomponents of the MS system (e.g., ion source, mass analyzer(s), iondetector); reducing or removing non-analytes such as matrix componentsthat have accumulated in the MS system after sample analysis, or thatare accumulating in the MS system during sample analysis; preventingfurther accumulation of non-analytes during a sample analysis;accelerating the conditioning of the MS system after a vent/pump-downprocedure; and restoring or creating an ion source condition (e.g.,surface oxidation state or other surface metric) more optimal orconsistent for MS analysis. The inventors have found hydrogen to behighly effective as a conditioning agent in an MS environment. Hydrogenrapidly diffuses and displaces surface contaminants. Hydrogen whendissociated or in higher excited, meta-stable or pseudo-Rydberg states(such as by electron impact or other processes) is very active and canreduce many adsorbed compounds, such as those that tend to becomeadsorbed on ion source surfaces and degrade operation. Moreover,hydrogen can alter metal oxidation states. The metal surfaces of an MSsystem are known to participate in a variety of reactions that affectthe analytes and other introduced compounds, such as dehydration orreduction as occur in the ion source. By converting the metals from arange of oxidation states to a reproducible and fixed set, performancecan be made more consistent. In the case of the ion source, spectralcharacteristics can be greatly stabilized. These conditioning attributesof hydrogen have not been fully appreciated by previous researchers, dueto the above-noted challenges attending the use of hydrogen. Moregenerally, the concept of adding a conditioning gas to an MS system hasnot been adequately investigated prior to the present work. This may beevidenced by the observation that, to date, efforts made toward improvedconditioning techniques have largely been limited to enhancing theremovability of components to facilitate conventional ex situcleaning—that is, shutting down the MS system physically removingcomponents from the MS system for the purpose of cleaning them—as wellas exploring alternative compositions of surfaces of the ion source inan attempt to reduce the need for conventional ex situ cleaning.

Generally, the conditioning gas may be any gas suitable for performingone or more of the foregoing functions in an MS system or exhibiting thesame or similar conditioning attributes as hydrogen. Thus, in additionto hydrogen, other examples of conditioning gases include, but are notlimited to, argon, fluorine, oxygen, ammonia, methane, and combinationsof two or more of hydrogen, argon, fluorine, oxygen, ammonia andmethane. The specific conditioning gas(es) utilized may depend onwhether the conditioning process is performed in an on-line mode oroff-line mode; these modes are described below. The conditioning gas maybe a single gas or a mixture of gases provided by gaseous or volatileliquid sources. In the present context, the term “gas” encompasses theterm “vapor.” The conditioning gas introduced into the MS system may bein addition to any other intentionally added gases such as, for example,a carrier gas for chromatography, reagent gases for chemical ionization,and collision gases for ion fragmentation in a collision cell or iontrap or for collisional cooling in an ion guide or ion trap.Alternatively, the conditioning gas may be added exclusively dependingon its nature and the specific state of the MS system. The conditioninggas added to the MS system may be part of a blend that includes acarrier gas or some other gas (e.g., an auxiliary gas as describedfurther below). Depending on the type of conditioning gas, theparticular embodiment being implemented, or the stage of the MS systemat which the conditioning gas is present, the conditioning gas moleculesmay be heated, electrically neutral, in a metastable, Rydberg or otherexcited state, or ionized.

In some embodiments, the MS system that is configured for carrying outin situ conditioning is part of a gas chromatograph/mass spectrometer(GC/MS) system and thus is interfaced with a gas chromatograph (GC). Insuch embodiments, the conditioning gas may be routed through a part ofthe GC prior to being introduced into the MS system. In someembodiments, the conditioning gas is introduced directly into the ionsource. Moreover, the conditioning gas may be introduced into one ormore locations of the MS system and/or the GC. For this purpose, morethan one discrete source of conditioning gas (or at least more than oneconditioning gas line) may be utilized.

In some embodiments, the MS or GC/MS system is configured for carryingout an off-line conditioning mode. In the off-line conditioning mode,the conditioning gas is introduced into the MS or GC/MS system during atime when the MS or GC/MS system is not being operated in an analyticalmode, i.e., is not being operated to perform mass spectrometry or gaschromatography/mass spectrometry on a sample to acquire analytical data.In such embodiments, the MS or GC/MS system may be configured to switchbetween the analytical mode and the conditioning mode. Execution of theswitch from one mode to the other may be entirely or partially manual,or entirely or partially automated such as in response evaluating one ormore parameters as described further below. Generally, in the off-linemode, conditioning gas may added during any stage of operation notinvolving the acquisition of analytical data on a sample, such aswarm-up, tuning, pump-down, venting, cool-down, etc. Moreover, theoff-line mode may entail adding the conditioning gas while one or morecomponents (e.g., the ion source) of the MS or GC/MS system are removed.

In other embodiments, the MS or GC/MS system is configured for carryingout an on-line (or dynamic) conditioning mode. In the on-lineconditioning mode, the conditioning gas is introduced into the MS orGC/MS system while the MS or GC/MS system is being operated to performmass spectrometry or gas chromatography/mass spectrometry on a sample.One or more parameters associated with the on-line conditioning mode maybe adjusted dynamically in response to the operating conditions of theMS or GC/MS system. In some embodiments, the MS or GC/MS system isconfigured for carrying out both the off-line and on-line conditioningmodes.

In addition to flowing the conditioning gas into the MS system, theconditioning mode may include maintaining one or more regions of the MSsystem or GC/MS system being subjected to the conditioning gas (e.g.,ion source, mass analyzer, ion detector, column) at a desiredtemperature or within a desired temperature range. The conditioningprocess may be enhanced by heating the conditioning gas and/or thesurfaces being treated by the conditioning gas. In addition, theconditioning mode may include operating the ion source to emit electronsinto the ionization chamber. The presence of the electrons may enhancethe conditioning process by one or more mechanisms, such as “activating”or generating secondary species from the conditioning gas that promotethe cleaning of surfaces.

In another embodiment, a conditioning gas such as hydrogen is utilizedas a carrier gas for transporting a sample through a GC column insteadof a more traditional carrier gas such as helium. An auxiliary gas, suchas helium, is added to the stream of hydrogen carrier gas at some pointupstream of the ion source, and the mixed gas flow enters the ionsource. This configuration has also been found to be effective as anon-line conditioning technique.

In the context of the present disclosure, the term “conditioning”generally refers to cleaning or otherwise bringing an ion source and/orother components or regions of a mass spectrometer to a condition thatimproves or optimizes the performance of the mass spectrometer. In oneaspect, conditioning is accomplished by operating the MS system to flowa conditioning gas into a mass spectrometer of the MS system. Theaddition of the conditioning gas in the mass spectrometer does notsubstantially change the mass spectral characteristics (or spectralresponse) of analytes of a sample being analyzed by the MS system duringan on-line conditioning process, or of a sample that would be analyzedby the MS system after an off-line conditioning process. That is, thespectral characteristics of the analytes remain substantially unchangedwith or without the addition of the conditioning gas. Stated in anotherway, the conditioning gas does not substantially change the ionabundance ratios of analytes. Instead, the conditioning gas cleans themass spectrometer and keeps non-analytes from accumulating in the massspectrometer. For these purposes, in a typical embodiment contemplatedfor the on-line conditioning mode, the conditioning gas may be, forexample, hydrogen, argon, or a blend (mixture) of hydrogen and argon. Inthe off-line conditioning mode, generally a wider range of conditioninggases are contemplated such as, for example, hydrogen, argon, fluorine,oxygen, ammonia, and/or methane.

The conditions or parameters under which the conditioning gas is addedmay be controlled to enable the conditioning gas to effect conditioningwithout substantially changing analyte spectral response. As an example,the concentration of the conditioning gas in the mass spectrometer maybe controlled, such as by regulating the flow rate of the conditioninggas into the mass spectrometer. Regulation of the flow rate of theconditioning gas may be relative to other gases being flowed into themass spectrometer. Other conditions or parameters may include thetemperature of the conditioning gas, the temperature and/or pressure inthe region or component of the mass spectrometer in which theconditioning gas is being utilized, and the extent to which theconditioning gas has been made energetic such as through operation ofthe ion source.

It thus can be seen that because the addition of the conditioning gasdoes not substantially change analyte spectral response, the addition ofthe conditioning gas does not cause chemical ionization (CI).Accordingly, in the context of the present disclosure, the conditioninggas is not a CI reagent gas.

In some embodiments in which the MS system includes a GC, theconditioning gas may be added to the mass spectrometer by flowing theconditioning gas through the analytical column of GC. It will beunderstood, however, that process of “conditioning” the massspectrometer as taught in the present disclosure is not the same as theprocess of “conditioning” or “pre-conditioning” the analytical column.Conditioning or pre-conditioning the analytical column typicallyinvolves running a solvent through the column to activate components ofthe stationary phase and/or purging the column of impurities inpreparation for a chromatographic experiment, and hence is a separateand different process unrelated to the presently disclosed conditioningprocess.

FIG. 1 is a schematic view of an example of a mass spectrometer (MS)system 100. The MS system 100 may generally include a mass spectrometer104 and a conditioning gas system 108. The mass spectrometer 104 mayinclude a sample source, a sample (or sample/carrier gas) inlet orinterface 112, an MS housing 116, an ionization apparatus (or ionsource) 120, a mass analyzer 124, an ion detector 128, and a vacuumsystem 132.

The sample source may be any device configured for providing a stream ofsample material to the ion source 120 via the sample interface 112. Asexamples, the sample source may be associated with a batch volume, asample probe, or a liquid handling system. The flow of the samplematerial to the ion source 120 may be effected by any means, such aspumping, capillary action, or an electrically-assisted technique. Inhyphenated techniques, the sample source may be associated with theoutput of an analytical separation instrument such as a gaschromatograph (GC) instrument, a liquid chromatographic (LC) instrument,a capillary electrophoresis (CE) instrument, a capillaryelectrochromatography (CEC) instrument, or the like. In someembodiments, the sample may be introduced or loaded directly into theion source 120, without having to flow the sample from a sample sourceand through a column or conduit. In these embodiments, the sample inletor sample interface to the ion source 120 may be, for example, a directinsertion probe. Depending on the technique employed to introduce thesample directly into the ion source, a carrier gas may or may not beutilized to assist in the sample introduction.

The ion source 120 may be any apparatus suitable for producing analyteions from a sample stream received from the sample source and directingthe as-produced ions into the mass analyzer 124. For example, the ionsource 120 may be an electron impact (EI) apparatus or a chemicalionization (CI) apparatus. The ion source 120 may also include thecapability of switching between EI and CI modes of operation. The ionsource 120 includes an ionization chamber 136 and an ionization device140. In the case of EI or CI, the ionization device 140 is typically afilament configured for emitting electrons in a manner understood bypersons skilled in the art. The present disclosure, however, is notlimited to EI and CI, and may encompass various other modes ofionization now known or later developed. In some embodiments, the ionsource 120 is not one that ionizes samples with plasma, such as aninductively coupled plasma (ICP) ion source, particularly for operatingthe on-line methods.

In the case of CI, the MS system 100 additionally includes a CI reagentgas source 144 that typically communicates with a conduit 148 of thesample interface 112 via a reagent gas line 152. The reagent gas source144 may represent one or more containers for supplying one or moredifferent types of reagent gases. The reagent gas may be any gassuitable for conducting CI in the ionization chamber 136 as appreciatedby persons skilled in the art. Examples of reagent gases include, butare not limited to, methane, isobutane, ammonia, carbon dioxide,dichlorodifluoromethane, trimethylsilane, nitric oxide, and methylamine. The flow of the reagent gas may be controlled by any means, suchas a gas flow controller (or flow control module) 156. The flowcontroller 156 may, for example, include one or more valves,restrictors, mass flow controllers, pressure regulators, or the like.The flow controller 156 may be manually or electronically controlled. Insome embodiments, the flow controller 156 may be a programmableelectronic pneumatic controller (EPC) of known design and operation. Inthe illustrated example, the reagent gas is supplied to the ionizationchamber 136 via a reagent gas path that runs from the reagent gas source144, through the reagent gas line 152 to the flow controller 156,through an auxiliary gas line 160 to the conduit 148 (via a port of theconduit 148), and into the ionization chamber 136.

The mass analyzer 124 may be any device configured for separating,sorting or filtering analyte ions on the basis of their respectivemasses (i.e., mass-to-charge ratios, or m/z ratios). Examples of massanalyzers 124 include, but are not limited to, multipole electrodestructures (e.g., mass filters, ion traps), time-of-flight (TOF)components, electrostatic analyzers (ESAs), and magnetic sectors. Themass analyzer 124 may include a system of more than one mass analyzer,particularly when ion fragmentation is desired. As examples, the massanalyzer 124 may be a tandem MS or MS^(n) system, as appreciated bypersons skilled in the art. As another example, the mass analyzer 124may include a mass filter followed by a collision cell, which in turn isfollowed by another mass filter. As another example, the mass analyzer124 may comprise an ion mobility spectrometer (IMS). In someembodiments, however, the MS system 100 does not comprise an IMS.

The ion detector 128 may be any device configured for collecting andmeasuring the flux (or current) of mass-discriminated ions outputtedfrom the mass analyzer 124. Examples of ion detectors 128 include, butare not limited to, electron multipliers, photomultipliers, and Faradaycups.

The ion source 120, mass analyzer 124, and ion detector 128 are disposedin the MS housing 116 with which the vacuum system 132 is interfaced.The MS housing 116 and vacuum system 132 are structured to definesuccessive vacuum stages in the mass spectrometer 104. By thisconfiguration the ion source 120, depending on design, is maintained ata desired low pressure or vacuum level, and the mass analyzer 124 andion detector 128 are maintained at desired vacuum levels. For a massanalyzer 124 that includes multiple components or modules such as notedabove, each component or module may be maintained at a different vacuumlevel. As an example, a collision cell is typically held at a higherpressure than the evacuated mass filters that precede or succeed thecollision cell. For the foregoing purposes, the vacuum system 132typically includes one or more vacuum pumps that communicate with one ormore vacuum stages via one or more exhaust ports of the MS housing 116.

The mass spectrometer 104 may also include a heating system 164. Theheating system 164 may include one or more heating devices configuredfor controlling the respective temperatures of one or more components ofthe mass spectrometer 104, such as the sample interface 112, ionizationchamber 136, mass analyzer 124, and ion detector 128. A given heatingdevice may be configured for direct heating such as a resistive heatingelement, or indirect heating such as system for routing a heatexchanging medium.

The MS system 100 may also include a system controller (or systemcontrol module) 168. The system controller 168 may be configured forcontrolling and/or monitoring various aspects of the MS system 100, suchas sample introduction into the ionization chamber 136, reagent gasintroduction (if applicable) and selection of reagent gases, sampleionization, selection of EI or CI modes of operation, vacuum andpressure settings, temperature settings or varying temperature profilesimplemented by the heating system 164, operating parameters of the massanalyzer 124 (e.g., applied electric and/or magnetic fields,collision/background gas introduction, timing of ion optics, and thelike), acquisition and analysis of signals from the ion detector 128,generation and display of mass spectra or chromatograms, and so on. Forthese purposes, the system controller 168 is schematically illustratedas being in signal communication with the mass spectrometer 104 via acommunication link 172. The communication link 172 may be representativeof several communication links respectively interfacing with variouscomponents of the MS system 100. A given communication link may be wiredor wireless. Also for these purposes, the system controller 168 mayinclude one or more types of hardware, firmware and/or software, as wellas one or more types of memory. In the illustrated example, the systemcontroller 168 includes an electronic processor 176, a database 180stored in memory, gas flow control software 184, and performanceevaluation software 188, as described further below. The systemcontroller 168 may also be representative of one or more types of userinterface devices, such as user input devices (e.g., keypad, touchscreen, mouse, and the like), user output devices (e.g., display screen,printer, visual indicators or alerts, audible indicators or alerts, andthe like), a graphical user interface (GUI) controlled by software, anddevices for loading media readable by the electronic processor 176(e.g., logic instructions embodied in software, data, and the like). Thesystem controller 168 may include an operating system (e.g., MicrosoftWindows® software) for controlling and managing various functions of thesystem controller 168. One or more components of the system controller168 may be located remotely from the MS system 100 and communicate withthe local portion of the system controller 168 over a wired or wirelesscommunication link. In some embodiments, the system controller 168 mayinclude or be part of a laboratory information management system (LIMS),e.g., as may be utilized in a hospital or other medical setting.

The conditioning gas system 108 is configured for directing aconditioning gas into the MS system 100. For this purpose, theconditioning gas system 108 may include a conditioning gas source incommunication with a conditioning gas line, and a gas flow controller asappropriate. As noted above, the conditioning gas may be, for example,hydrogen, argon, ammonia, and/or methane. The conditioning gas system108 may be configured for directing the conditioning gas to one or morelocations of the MS system 100. Various alternatives are depicted bydashed blocks and lines in FIG. 1. Thus, in one embodiment, aconditioning gas source 204 and an associated conditioning gas line 208communicate with the gas flow controller 156 that also regulates theflow of reagent gas from the reagent gas source 144. In this embodiment,the conditioning gas is flowed into the auxiliary gas line 160, throughthe conduit 148 and into the ionization chamber 136. In anotherembodiment, a conditioning gas source 212 and an associated conditioninggas line 216 communicate directly with the ionization chamber 136,whereby the conditioning gas is flowed directly into the ionizationchamber 136. In another embodiment, the conditioning gas source 212 andan associated conditioning gas line 220 communicate directly with themass analyzer 124, or with one or more components of a multi-componentmass analyzer 124. For instance, the conditioning gas may be introducedinto a collision cell, a mass filter, an ion guide, or two or more ofsuch mass analyzer components. In another embodiment, the conditioninggas source 212 and an associated conditioning gas line 224 communicatedirectly with an appropriate region of the ion detector 128. Theconditioning gas system 108 may include a single conditioning gas source212 that communicates with one of the foregoing locations, or mayinclude two or more conditioning gas sources 212 (or at least two ormore conditioning gas lines 216, 220, 224) that respectively communicatewith two or more of the foregoing locations. It will be noted that oneconditioning gas source 212 is illustrated in FIG. 1 for simplicity;each of the conditioning gas lines 216, 220, 224 may be associated witha different conditioning gas source. It will also be noted that a gasflow controller (not shown) may be placed in communication with one ormore of the conditioning gas lines 216, 220, 224, and may have the sameor similar configuration as the gas flow controller 156 associated withthe reagent gas source 144. Any of the gas flow controllers provided inthe MS system 100 may be manually operated and/or controlled by thesystem controller 168, such as by the electronic processor 176 inaccordance with instructions provided by the gas flow control software184.

In all of the foregoing embodiments, the conditioning gas system 108provides a conditioning gas flow path from the conditioning gassource(s) 204 and/or 212, through the conditioning gas line(s) 208, 216,220 and/or 224, and into the mass spectrometer 104. The conditioning gasflow path runs either directly into one or more locations of the massspectrometer 104 or from a location upstream of the mass spectrometer104. In any of these embodiments, the conditioning gas may flow ordiffuse from the MS component into which it first directly entered toone or more of the other MS components. For example, the conditioninggas supplied directly into a collision cell may flow or diffuse to apreceding and/or succeeding mass filter. For another example, theconditioning gas supplied directly into a component of the mass analyzer124 may flow or diffuse into the ionization chamber 136 and/or the iondetector 128. In some embodiments (described further below), theconditioning gas flow path may be established while the MS system 100 isbeing actively operated in an analytical mode, i.e., while sample andion flow paths are established in a direction generally from theionization chamber 136 toward the mass analyzer 124. Even in theseembodiments, a sufficient amount of the conditioning gas injecteddirectly into the mass analyzer 124 may diffuse in the oppositedirection into the ionization chamber 136 and be effective forconditioning/cleaning surfaces of the ionization chamber 136.

FIG. 1 also illustrates an embodiment in which the MS system 100includes a gas chromatograph (GC, or GC system) 230 or, stateddifferently, is part of a gas chromatograph/mass spectrometer (GC/MS)system. In such an embodiment, the MS system 100 may alternatively becharacterized as being interfaced with the GC 230 via the sampleinterface 112, which in this case may also be termed a GC/MS interface.The GC 230 may generally include a GC housing 234, a sample introductiondevice 238 typically mounted at the GC housing 234, a carrier gas source242, a column (or GC column) 246 disposed in the GC housing 234, and aheating device 250.

The column 246 includes a column inlet 252 communicating with the sampleintroduction device 238 via a sealed fluid connector, and a columnoutlet 254 communicating with the ionization chamber 136. A portion ofthe column 246 may extend through the sample interface 112 and into theionization chamber 136, such that the column outlet 254 is located inthe ionization chamber 136. Alternatively or equivalently, the column246 may be coupled to a transfer line via a sealed fluid connector, inwhich case the transfer line extends through the sample interface 112and into the ionization chamber 136. The column 246 includes astationary phase, which typically comprises a liquid or polymer held ona solid support or film lining the inside wall of the column 246. Avariety of compositions may be selected for the stationary phase, and arange or porosities or densities may be selected for the stationaryphase, as appreciated by persons skilled in the art. To conserve spacewhile maintaining a desired length, the column 246 may include a coiledsection 256.

The sample introduction device 238 typically includes a device forinjecting the sample into the column inlet 252, and may include a devicefor vaporizing the sample. The sample may be a matrix that includessample material to be analytically separated in the column 246 and oneor more solvents. The sample introduction device 238 may be in fluidcommunication with a separate sample source (not shown) or may functionas the sample source. For instance, the sample introduction device 238may be configured to receive one or more sample containers 260, and mayinclude a device (e.g., a carousel) for selecting a desired sample forinjection into the column 246.

The carrier gas source 242 may communicate with the column inlet 252 viaa carrier gas line 264. The carrier gas line 264 may be coupled to aportion of the sample introduction device 238 at a point upstream of thecolumn inlet 252. The carrier gas may be any gas suitable for serving asan inert mobile phase that facilitates transport of the sample throughthe column 246 as appreciated by persons skilled in the art. Examples ofcarrier gases include, but are not limited to, helium, nitrogen, argon,or in some embodiments hydrogen. The flow of the carrier gas may becontrolled by any means, such as a gas flow controller 268. The flowcontroller 268 may have the same or similar configuration as the flowcontroller 156 associated with the reagent gas source 144. In theillustrated example, the carrier gas is supplied to the column 246 via acarrier gas path that runs from the carrier gas source 242, through thecarrier gas line 264 to the flow controller 268, and into the columninlet 252 (possibly via the sample introduction device 238 as notedabove).

The heating device 250 may have any configuration suitable formaintaining the column 246 at a desired temperature setting or forvarying the temperature of the column 246 according to a desired (i.e.,predetermined) temperature profile (or temperature program). In oneexample, the GC housing 234 is (or contains) an oven, and the heatingdevice 250 is configured for heating the interior of the oven throughwhich the column 246 extends. In another example, the heating device 250is configured for heating the column 246 directly. For instance, theheating device 250 may include a resistive heating element mounted inthermal contact with the column 246.

When the GC is included, the MS system 100 may also include additionalmeans for analyzing the components of the sample that are separated bythe column 246, i.e., an analyzing instrument that is in addition to themass spectrometer 104. Thus, in the illustrated embodiment the MS system100 includes an optional gas detector 272 of any suitable type, which istypically positioned outside the GC housing 234. The gas detector 272may be the type capable of producing a spectrum or chromatogram, such asa flame ionization detector (FID) or thermal conductivity detector(TCD). The gas detector 272 may communicate with a section 276 of thecolumn 246 between the coiled section 256 and the column outlet 254 viaa gas outlet line 278. A flow splitter (not shown) may be locatedin-line with the column 246 at this section 276 for this purpose. Bythis configuration, the sample/gas flow in the column 246 from thecoiled section 256 is split into a first output flow directed into theionization chamber 136 and a second output flow directed via the gasoutlet line 278 into the gas detector 272.

With the GC 230 coupled to the MS system 100, additional embodiments arepresented for configuring the conditioning gas system 108 to directconditioning gas into the MS system 100. Generally, these additionalembodiments entail introducing the conditioning gas at one or morelocations upstream of the ionization chamber 136, by establishing one ormore conditioning gas flow paths that run at least partially through theGC housing 234. In some embodiments, the conditioning gas flow path(s)may run through at least a portion of the column 246. Variousalternatives are depicted by dashed blocks and lines in FIG. 1. Thus, inone embodiment, a conditioning gas source 282 and an associatedconditioning gas line 284 communicate with the gas flow controller 268that also regulates the flow of carrier gas from the carrier gas source242. In this embodiment, the conditioning gas is flowed from the flowcontroller 268 into a common gas inlet line 286 and into the columninlet 252. The flow controller 268 may be utilized to regulate therespective flows (e.g., flow rates) of the carrier gas and theconditioning gas into the column 246. Depending on the particularconditioning strategy being implemented, the proportion of the carriergas relative to the conditioning gas flowing into the column 246generally ranges from 0% to less than 100% by volume. That is, the flowcontroller 268 may be operated to shut off the flow of carrier gascompletely while the conditioning gas is flowed into the column 246, orto mix the carrier gas and the conditioning gas wherein both gases flowthrough the gas inlet line 286 in desired proportions. In anotherexample, the proportion of the conditioning gas in the mixed flow rangesfrom 0.02% to 50%. In another example, the proportion of theconditioning gas ranges from 0.05% to 40%. In another example, theproportion of the conditioning gas ranges from 0.25% to 10%. Theseexemplary ranges may be employed in other embodiments in which theconditioning gas is introduced elsewhere in the MS system 100, and moregenerally apply to regulating the flow of conditioning gas into the massspectrometer 104. Moreover, these exemplary ranges may be employed invarious embodiments entailing either on-line mode or off-line mode.

In another embodiment, a conditioning gas source (not shown) andassociated conditioning gas line (not shown) communicate with a section(not shown) of the column 246 between the column inlet 252 and thecolumn outlet 254, such as between the column inlet 252 and the coiledsection 256, at the coiled section 256, or between the coiled section256 and the column outlet 254. By way of example, in FIG. 1 aconditioning gas source 290 and associated conditioning gas line 292communicate with a section 296 of the column 246 between the coiledsection 256 and the column outlet 254 (or between the coiled section 256and the sample interface 112). Any structure or device suitable formerging the respective gas flows at a desired column section may beutilized, such as a tee connection, a union, or the like. As in otherembodiments, a suitable flow controller 304 may be provided in-line withthe conditioning gas line 292 to regulate the flow of conditioning gas.As in other embodiments in which the conditioning gas is added to thecarrier gas, the proportion of the conditioning gas may be regulated inaccordance with the examples of ranges set forth above.

The conditioning gas system 108 may include a single conditioning gassource that communicates with one of the foregoing locations of the GC230, or may include two or more conditioning gas sources (or at leasttwo or more conditioning gas lines) that respectively communicate withtwo or more of the foregoing locations of the GC 230, or with two ofmore of the above-described locations of the GC 230 and the MS system100. As in the case of other flow controllers described above, any ofthe flow controllers (e.g., 268, 304) associated with the GC 230 may bemanually operated and/or controlled by the system controller 168, suchas by the electronic processor 176 in accordance with instructionsprovided by the gas flow control software 184.

In some embodiments, a given conditioning gas source 204, 212, 282, 290may include a blend of the conditioning gas and an auxiliary gas. Forexample, the conditioning gas source 204, 212, 282, 290 may be providedin the form of a single tank that contains the blend, such that the MSsystem 100 does not need to provide a device for mixing the conditioninggas and the auxiliary gas together. The proportion of the conditioninggas relative to the auxiliary gas contained in the conditioning gassource 204, 212, 282, 290 may range from 0% to less than 100% by volume.In another example, the proportion of the conditioning gas relative tothe auxiliary gas ranges from 0.05% to 20%. In another example, theproportion of the conditioning gas relative to the auxiliary gas rangesfrom 0.25% to 10%. The composition of the auxiliary gas may be the sameas or different from that of the carrier gas being utilized. Theauxiliary gas may generally be any inert gas (i.e., a gas that does notreact with the sample or otherwise adversely affect the performance ofthe mass spectrometer 104) that is different from the conditioning gas.Examples of auxiliary gases include, but are not limited to, helium,nitrogen, and argon. The composition of the auxiliary gas may be thesame as that of the carrier gas also being utilized in the MS system100, or may be different. Some examples of uses of the auxiliary gas aredescribed in the EXAMPLES below.

In another embodiment, an auxiliary gas source 308 and associatedauxiliary gas line 310 are provided to enable the conditioning gas to beblended with the auxiliary gas. Thus, the flow controller 304 may beconfigured for regulating the respective flows of the auxiliary gas andthe conditioning gas such that the proportion of the auxiliary gasrelative to the conditioning gas in the mixed flow ranges from 0% toless than 100% by volume. In another example, the proportion of theauxiliary gas relative to the conditioning gas ranges from 0.05% to 80%.In another example, the proportion of the auxiliary gas relative to theconditioning gas ranges from 0.25% to 20%. In the illustrated example,the auxiliary gas line 310 communicates with the flow controller 304with which the conditioning gas source 290 also communicates. In thisexample, the conditioning gas—or a blend or mixture of the conditioninggas and the auxiliary gas—is flowed to the column section 296 via acommon gas inlet line 314. It will be understood that any of the otherconditioning gas sources described herein and/or illustrated in FIG. 1may likewise be associated with an auxiliary gas source for establishinga mixed flow of conditioning gas and auxiliary gas to a given locationof the MS system 100.

In addition to interfacing with components of the mass spectrometer 104and the conditioning gas system 108, the system controller 168 may beconfigured for controlling and/or monitoring various aspects of the GC230, such as sample introduction into the column 246, column leakageevents, pressure settings, temperature settings or varying temperatureprofiles implemented by the heating device 250, operation of the gasdetector 272 (if provided), acquisition and analysis of signals from thegas detector 272, generation and display of spectra or chromatogramsderived from the gas detector 272, and so on. For these purposes, thesystem controller 168 is schematically illustrated as being in signalcommunication with the GC 230 via a communication link 318, which may bewired or wireless and may represent one or more dedicated communicationlinks to individual components of the GC 230. It can be seen that thesystem controller 168 schematically depicted in FIG. 1 may represent oneor more means or devices for coordinating or synchronizing the variousoperations of the mass spectrometer 104 and the GC 230, as well as theconditioning gas system 108.

The MS system 100 includes means (or apparatus) for operating the MSsystem 100 in an analytical mode. In the analytical mode, the MS system100 processes one or more samples to produce one or more mass spectra orchromatograms from which information regarding analytes of the sample(s)may be obtained. In some embodiments, the means for operating in theanalytical mode may be configured for establishing a sample flow paththrough the sample interface 112 and into the ionization chamber 136. Asan example, the sample is introduced into the ionization chamber 136 andthe ionization device 140 operated to produce analyte ions from thesample. The analyte ions are transported into the mass analyzer 124,which sorts the ions according to mass—and, depending on design,possibly performs one or more iterations of ion fragmentation—asappreciated by persons skilled in the art. The resultingmass-discriminated ions are then transported to the ion detector 128,which is typically configured to convert the ion currents intoelectrical signals. The electrical signals are transmitted to a dataanalyzer, schematically represented by the system controller 168, forprocessing and generation of a mass spectrum or chromatogram.Accordingly, the means for operating in the analytical mode may includeone or more of the following components: the sample interface 112; theionization chamber 136; other components of the MS system 100 utilizedin the processing of samples and production of mass spectra orchromatograms; one or more gas flow controllers as needed, which may beoperated by manual (user) input, or may be semi-automated or fullyautomated by electronic or computerized control; and/or electronichardware, firmware and/or software modules as schematically representedby the system controller 168 in FIG. 1. Manual input may entailphysically manipulating a valve or other device. Manual input mayalternatively or additionally entail pushing a button, operating aswitch, or entering information on a control panel that communicateswith or is associated with the system controller 168, in response towhich the electronic processor 176 or other component of the systemcontroller 168 transmits a control signal to an appropriate component ofthe means for operating in the analytical mode.

In embodiments in which the MS system 100 is interfaced with the GC 230,the analytical mode may include operating the sample introduction device238 to inject a sample and carrier gas into the column 246, therebyestablishing a flow of the sample and carrier gas through the column246. In this case, the sample (or sample/carrier gas) flow path isdefined in part by the column 246. Different components of the sampleare separated by the stationary phase of the column 246 according toknown chromatographic retention principles, and the resulting mixture ofseparated analyte fractions and carrier gas is flowed through the column246, through the sample interface 112, and into the ionization chamber136. The sample is then processed in the MS system 100 in the mannerdescribed above. Accordingly, in these embodiments the means foroperating in the analytical mode may include one or more of thefollowing components: the sample introduction device 238, the carriergas source 242; the carrier gas line 264; and/or the column 246.

The MS system 100 also includes means (or apparatus) for operating theMS system 100 in a conditioning mode. In the conditioning mode, the MSsystem 100 is operated to flow a conditioning gas into the massspectrometer 104 via one or more conditioning gas flow paths describedabove. In some embodiments, the means for operating in the conditioningmode may be configured for establishing a conditioning gas flow pathfrom the conditioning gas source 204 and/or 212, through theconditioning gas line 208, 216, 220 and/or 224, and into the massspectrometer 104. Accordingly, the means for operating in theconditioning mode may include one or more of the following components:the conditioning gas system 108, the conditioning gas source 204 and/or212; the conditioning gas line 208, 216, 220 and/or 224, and any othergas conduits as needed to route the conditioning gas to one or moredesired locations of the mass spectrometer 104; one or more gas flowcontrollers (e.g., 156) as needed, which may be manually operated,semi-automated or fully automated as described above; and/or electronichardware, firmware and/or software modules as schematically representedby the system controller 168 in FIG. 1. In embodiments in which the MSsystem 100 is interfaced with the GC 230, the means for operating in theconditioning mode may include alternative or additional conditioning gassources 282 and/or 290, associated conditioning gas lines 284 and/or 292and any other gas conduits as needed; and/or other flow controllers(e.g., 268, 304). The means for operating in the conditioning mode mayalso include one or more auxiliary gas sources 308 and associatedauxiliary gas lines 310 as described above.

In some embodiments, the effectiveness of the conditioning gas may beoptimized by adding thermal energy to the conditioning gas and/orcontrolling its temperature. Accordingly, depending the conditioning gasflow path through the MS system 100, the means for operating in theconditioning mode may also be configured for controlling one or more ofthe following temperatures: the temperature of the column 246 and/or aninterior of the GC housing 234 (e.g., an oven); the temperature of thesample interface 112; the temperature of the ionization chamber 136; thetemperature of the mass analyzer 124; and/or the temperature of the iondetector 128. Temperature control may thus be accomplished by operatingthe heating device 250 and/or the heating system 164, which may becontrolled by the system controller 168 and may follow a programmedtemperature profile. In one example, the means for operating in theconditioning mode is configured for maintaining the ionization chamber136 at a temperature up to the failure limits of the metal surfaces ofthe ionization chamber 136. In another example, the means for operatingin the conditioning mode is configured for maintaining the ionizationchamber 136 at a temperature ranging from −20° C. to 800° C.

In some embodiments, the effectiveness of the conditioning gas may beoptimized by adding energy to the conditioning gas to excite (orenergize) the conditioning gas molecules to an energetic state (e.g., aRydberg or metastable state) or to ionize the conditioning gasmolecules. The ionization device 140 may, for example, be operated forthis purpose to produce electrons that interact with the conditioninggas molecules.

The means for operating the MS system 100 in the conditioning mode maybe configured for regulating respective flows (e.g., flow rates) of thecarrier gas and the conditioning gas into the column inlet 252 or intothe mass spectrometer 104). The proportion of the carrier gas relativeto the conditioning gas flowing into the column inlet 252 may range from0% to less than 100%. Alternatively or additionally, the means foroperating the MS system 100 in the conditioning mode may be configuredfor regulating respective flows of the auxiliary gas and theconditioning gas. The proportion of the auxiliary gas relative to theconditioning gas flowing through a particular gas line may range from 0%to less than 100%. The means for operating the MS system 100 in theconditioning mode may configured for determining whether the MS system100 should be operated in the conditioning mode, or for regulatingrespective flows of the conditioning gas and the carrier gas into themass spectrometer 104, based on comparing a chromatogram produced fromthe ion detector 128 from an analysis of a sample with a chromatogramproduced from the gas detector 272 from the same analysis.

The means for operating the MS system 100 in the conditioning mode maybe configured for off-line operation, on-line operation, or both. Inoff-line embodiments, the means for operating in the conditioning modemay include means (or apparatus) for switching the MS system 100 betweenthe analytical mode and the conditioning mode. The means for switchingmay include one or more gas flow controllers and/or the systemcontroller 168 as described above.

The means for operating in the off-line conditioning mode may beconfigured for evaluating one or more parameters of the MS system 100and, based on the value of the parameter, determining whether the MSsystem 100 should be operated in the conditioning mode (or,equivalently, should be switched from the analytical mode to theconditioning mode). Examples of parameters that may be evaluatedinclude, but are not limited to, the number of times the MS system 100or a component thereof (e.g., mass spectrometer 104, ion source 120,column 246) has been operated in the analytical mode prior to evaluatingthe parameter (or since the last time the parameter was evaluated, orsince the last time the conditioning mode was implemented); the amountof time that has elapsed prior to evaluating the parameter (or since theparameter was last evaluated, or since the conditioning mode was lastimplemented); a quality of a chromatogram (or mass spectrum) produced bythe MS system under predetermined operating conditions; a measurement ofan abundance of ions of one or more selected mass-to-charge ratios takenwhile operating in the analytical mode or conditioning mode; and/or thepresence of stationary phase material separated from a stationary phasesupport of the column (i.e., evidence of column bleed). The quality ofthe chromatogram may include any metric (e.g., signal-to-noise ratio)indicative of a degradation in signal response or other performancecriterion of the MS system 100. Parameters such as the quality of thechromatogram and abundance of contaminant ions may be compared toreference parameters stored in the database 180 of the system controller168 to assist in the determination as to whether the conditioning modeshould be run. Measurements of the abundance of selected ions may bedone while operating in the conditioning mode to enable adjustment ofcertain operating parameters of the conditioning mode, such as the levelof conditioning gas being added. The evaluation of one or moreparameters of the MS system 100 for the purpose of determining whetherto operate in the conditioning mode may be performed or managed by theperformance evaluation software 188 of the system controller 168.

Alternatively or additionally, one or more of the above parameters maybe evaluated manually by a user of the MS system 100. As examples, theuser may keep track of the age and/or number of uses of one or morecomponents of the MS system 100 that are known to improve or restore theperformance of the MS system 100 after being subjected to theconditioning process. The user may make a visual inspection of achromatogram or mass spectrum obtained from a sample analysis or abackground analysis, and determine that the MS system 100 needs to beconditioned. Alternatively or additionally, the MS system 100 may beconfigured to enable the user to switch the MS system 100 to theconditioning mode at any desired time, or in accordance with apredetermined maintenance schedule.

If a determination is made that the MS system 100 should be operated inthe conditioning mode, the means for operating in the off-lineconditioning mode may be configured for taking an action based on (or inresponse to) that determination. As examples, the action may includeswitching the operation of the MS system 100 to the conditioning mode,scheduling a time for switching the operation of the MS system 100 tothe conditioning mode, modifying a pre-scheduled time for switching theoperation of the MS system 100 to the conditioning mode, and/orproducing a user-readable indication that the MS system 100 should beoperated in the conditioning mode. A user-readable indication mayinclude, for example, an audible or visual alarm, a visual indication ormessage displayed on a user control panel of the MS system 100 or on adisplay screen communicating with the MS system 100, an electronic mailmessage sent to a user, etc.

In on-line embodiments, the means for operating in the conditioning modemay include means (or apparatus) for regulating respective flows of thecarrier gas and the conditioning gas into the mass spectrometer 104while the MS system 100 is actively performing a sample analysis. Themeans for regulating may include one or more gas flow controllers and/orthe system controller 168 as described above. The means for regulatingmay be configured for regulating the respective flows such that theproportion of the conditioning gas flowing into the mass spectrometerranges from greater than 0% to less than 100% by volume. In anotherexample, the proportion of the conditioning gas ranges from 0.02% to50%. In another example, the proportion of the conditioning gas rangesfrom 0.05% to 40%. In another example, the proportion of theconditioning gas ranges from 0.25% to 10%. As previously notes, theseranges may also apply to the off-line mode. The means for regulating maybe configured for maintaining the flow of the conditioning gas at aconstant flow rate while the temperature of the column 246 is beingvaried directly or indirectly by the heating device 250. For example,the system controller 268 may monitor the temperature and cause one ormore flow controllers to adjust gas flow rate as needed.

Like the means for operating in the off-line conditioning mode describedabove, the means for regulating respective flows of the carrier gas andthe conditioning gas into the mass spectrometer 104 while in the on-linemode may be based on evaluating one or more parameters of the MS system100. In addition to the parameters described above, other examples ofparameters that may be evaluated include, but are not limited to, ameasurement of an abundance of ions of one or more selectedmass-to-charge ratios taken while the MS system 100 is being operated tomake a sample analysis; the composition of a sample matrix flowing or tobe flowed through the column 246; the composition of a stationary phasesupported in the column 246; an inside diameter of the column 246;and/or the reactivity of one or more components of the sample matrixwith the conditioning gas. As noted above, the evaluation of theparameter(s) may be assisted by the performance evaluation software 188and/or the use of data stored in the database 180 of the systemcontroller 168.

One of the challenges associated with adding a conditioning gas to theMS system 100 is knowing how the conditioning gas is being addedrelative to the carrier gas. This is especially true when implementinglower gas flows (e.g., 0.005 mL/min). In some embodiments, the relativeamount of added conditioning gas may be chosen based on the rate atwhich contaminant(s) is being introduced into the ion source 120. Ingeneral, larger amounts of conditioning gas are added for higher amountsof contaminant(s). For various experiments, particularly routineexperiments, it is desirable to be able to set the level of conditioninggas consistently. In some embodiments, the level of conditioning gas isset based on the ratio of the abundance of carrier gas to the abundanceof conditioning gas. In some embodiments, the amounts (e.g., flow rates,pressures) of conditioning gas and carrier gas are electronicallycontrolled by the MS system 100, such as by the system controller 168illustrated in FIG. 1. In such embodiments, the level of conditioninggas may be set automatically as part of an auto-tuning function of theMS system 100. FIG. 2 illustrates a mass spectral measurement of aconditioning gas (in this example, hydrogen, m/z=2) and a carrier gas(in this example, helium, m/z=4) being run through an MS system 100.Specifically, the measurement of FIG. 2 was obtained from the experimentdescribed in Example 7 below. Accordingly, the means for regulatingrespective flows of the carrier gas and the conditioning gas into themass spectrometer 104 may be configured for regulating based on adesired ratio of the abundance of conditioning gas ions to the abundanceof carrier gas ions as measured by operating the ion source 120, themass analyzer 124, and the ion detector 128. Moreover, the means forregulating the respective flows may be configured for comparing ameasured ratio of the abundance of conditioning gas ions to theabundance of carrier gas ions with the desired ratio to determinewhether a ratio difference between measured ratio and the desired ratiofalls outside a desired range, and adjusting the flow of theconditioning gas relative to the carrier gas into the mass spectrometer104 to maintain the ratio difference within the desired range. Desiredratios, for example, may be correlated to certain experiments, and/ordifferent stages of a given experiment, and provided in look-up tablesstored in the database 180 and accessible by hardware, firmware and/orsoftware components of the system controller 168.

In some embodiments, such as in EXAMPLE 8 below, a conditioning gas suchas hydrogen is utilized as the carrier gas for transporting the samplethrough the column 246, and an auxiliary gas such as helium is added tothe hydrogen or other carrier gas either upstream of or at the massspectrometer 104. The conditioning gas system 108 or other means ordevice may be utilized to regulate the flow of the auxiliary gas intothe mass spectrometer 104 relative to the flow of the conditioning gasinto the ionization chamber 136. Many of the above-described evaluationtasks may be performed in these embodiments. The mass spectrometer 104may be operated to measure a ratio of the abundance of carrier gas ionsto the abundance of auxiliary gas ions, and the flow of the auxiliarygas relative to the flow of the conditioning gas may be regulated basedon the measured ratio.

Example 1 Off-Line Conditioning

In this Example, a heavily-fouled MS system 100 consistent with thatshown in FIG. 1, and with a GC 230 connected thereto, was subjected toan off-line conditioning process. Hydrogen was selected as theconditioning gas. A stream of hydrogen was introduced through the portof the sample interface 112 normally utilized for CI reagent gas andthereby conducted into the ionization chamber 136 and quadrupole of themass spectrometer 104. The flow rate of the added hydrogen was 0.1mL/min. The temperature of the ion source was 350° C., and thetemperature of the quadrupole was 200° C. Hydrogen flow took place forsixteen hours, with the filament in continuous operation at 150 μA.Prior to conditioning the MS system 100 was run with the massspectrometer 104 active, but without a sample, to analyze the backgroundspecies suspected as contaminating the MS system 100. FIG. 3A is theresulting mass spectrum. The ion masses shown as being abundant arethose typically associated with non-analytical or background molecules.FIG. 3B is a background mass spectrum generated after conditioning. Atthe same scale as the spectrum of FIG. 3A, the background species (e.g.,m/z=45.1, 78.1, 134.9, etc.) appear to have been eliminated. FIG. 3C isthe same mass spectrum as FIG. 3B, but on an expanded scale. FIG. 3Cdemonstrates a significant reduction in the abundance of the backgroundspecies.

Example 2 Off-Line Conditioning

FIG. 4A is a Reconstructed Total Ion Chromatogram (RTIC, or TIC) as afunction of time (minutes) generated from running an MS system 100consistent with that illustrated in FIG. 1, without any conditioningprocess. FIG. 4A shows that without the conditioning process disclosedherein, continued use of the MS system 100 results in a slow improvementover a period of hours. As also shown in FIG. 4A, the system reaches anasymptotic state at which additional time of use leads to littleimprovement in background. FIG. 4B is another RTIC of the same MS system100, but after 240 minutes the MS system 100 was treated to the off-lineconditioning process for two hours using hydrogen as the conditioningagent. The background was then re-examined and found to have dropped by50-fold over the projected RTIC value, as shown in FIG. 4B. A subsequentconditioning process at 270 minutes provided a slight improvement, asalso shown in FIG. 4B.

Example 3 Off-Line Conditioning

FIGS. 5A-5E are ion chromatograms as a function of time for theindividual ion masses 55-u (from hydrocarbon substances in the MS system100), 105-u (from aromatic components), 91-u (from aromatic components),215-u (from heavier, sample matrix-related components), and 207-u (fromthe GC capillary column connected to the system), respectively. Thesechromatograms were generated from running an MS system 100 consistentwith that illustrated in FIG. 1, and treating the MS system 100 to theconditioning process after about 250 and 270 minutes. FIGS. 5A-5Edemonstrate that not all ions have the same origin or behavior under theconditioning process, such that monitoring and modification of theconditioning process in a given MS system 100 may be advisable. Thesmallest gains were achieved for the 207-u ion as this ion is constantlybeing renewed from the column, which suggests that the condition processshould be carried out more frequently to remove this component.

Example 4 Off-Line Conditioning

FIG. 6A is a reconstructed ion chromatogram for selected ion monitoring(SIM) acquisitions of octafluoronaphthalene in a contaminated MS system100. The analyte is barely discernable as a “bump” near 4.216 minutes,and as indicated by the signal-to-noise (S/N) ratio. FIG. 6B is areconstructed ion chromatogram for SIM acquisitions ofoctafluoronaphthalene in the same MS system 100 as in FIG. 6A, but aftertreatment to the off-line conditioning process using hydrogen as theconditioning agent. The background noise was significantly removed,leaving a clear peak without a tail, and a 50-fold increase in the S/Nis indicated. FIGS. 6A and 6B demonstrate that application of theconditioning process can enhance the detection of an analyte by loweringthe background around an ion of interest, or raising or restoringperformance.

Example 5 On-Line Conditioning

This Example describes an analysis of a sample of three n-alkanehydrocarbons in isooctane to test the effect of the addition of hydrogento the helium entering the mass spectrometer.

FIG. 7 is a schematic view of an example of an MS system 700 configuredin particular for on-line conditioning and utilized in this Example. TheMS system 700 includes many of the same components as the MS system 100illustrated in FIG. 1, although for simplicity some of these componentsare not illustrated in FIG. 7. As between FIG. 1 and FIG. 7, similarcomponents are designated by the same reference numerals. The MS system700 illustrated in FIG. 7 includes a mass spectrometer 104 and a GC 230connected thereto. The mass spectrometer 104 includes an ion source 120.The GC 230 includes a sample introduction device 238 equipped with asplit/splitless inlet 304, and a column 246. The MS system 700 furtherincludes a first flow controller 308 for the conditioning gas and anassociated conditioning gas line 310, a second flow controller 314 foran auxiliary gas and an associated auxiliary gas line 316, and thirdflow controller 320 and an associated gas outlet line 322. The flowcontrollers 308, 314, 320 utilized in this Example were programmableEPCs. The conditioning gas line 310 is connected to the auxiliary gasline 316 at a point outside the GC housing 234 by any suitable plumbingstructure such as a union (not shown). The gas outlet line 322 isconnected to the auxiliary gas line 316 at a point inside the GC housing234 by any suitable plumbing structure such as a union (not shown). Theoutlet of the column 246 is connected to a purged union 326. A gastransfer line 330 interconnects the purged union 326 and the ion source120. The gas transfer line 330 may be considered as an extension of thecolumn 246 or alternatively as a separate gas line.

In this Example, the carrier gas was helium, the conditioning gas washydrogen, and the auxiliary gas was helium. The helium carrier gas wassupplied to the inlet of the column 246 at a pressure of about 12.5 psi.The purged union 326 facilitated the addition of the stream of hydrogenand auxiliary helium to the sample/helium stream flowing from the column246. The first flow controller 308 supplied hydrogen at 10.12 psithrough a restrictor 334, after which the flow rate was 0.067 mL/min.The second flow controller 314 supplied helium at 3.76 psi at a flowrate of 8.9 mL/min to regulate the pressure in the purged union 326. Thethird flow controller 320 was plumbed backwards through a restrictor(not shown) into the mixed helium/hydrogen stream from the first andsecond flow controllers 308, 314 to vent part of the helium/hydrogenmixture (arrow 338) at a constant flow of 8.362 mL/min. The pressure ofthe helium/hydrogen mixture at the third flow controller 320 was 2.0psi. During the chromatographic run, the helium stream from the column246 flowed into the purged union 326 at a flow rate of 1.2 mL/min, andthe inlet pressure of the helium carrier gas into the column 246 and thepressures in the first and second flow controllers 308, 314 were allprogrammed to maintain constant flow at the above-indicated levelsthroughout the temperature program. With all flow controllers 308, 314,320 turned on, the helium/hydrogen mixture flowed into the purged union326 at flow rates of 0.6 mL/min (He) and 0.005 mL/min (H₂). Theresulting helium/hydrogen mixture entered the ion source 120 at 1.805mL/min. If the first flow controller 308 is turned off (i.e., withoutthe 0.005-mL/min hydrogen being a part of the stream entering the ionsource 120), then only the 1.8 mL/min of helium would enter the ionsource 120. Thus, by the configuration illustrated in FIG. 7, samplescan be easily run with or without implementing the conditioning processemployed in this Example (i.e., turning the hydrogen flow on or off).

To test the effect of the addition of hydrogen to the helium enteringthe mass spectrometer 104, multiple analyses of a sample of threen-alkane hydrocarbons—specifically n-tetradecane (n-C₁₄), n-pentadecane(n-C₁₅), and n-hexadecane (n-C₁₆)—in isooctane, each at a concentrationof 10 ng/μL, were performed both with and without the addition of thehydrogen. This sample was chosen because it is a high concentration ofrelatively non-polar compounds that exhibit very few if any activityproblems.

TABLE 1 below lists the instrument parameters for this Example.

TABLE 1 Instrument Parameters Ramp ° C./min ° C. Hold min Initial 90 0.5Ramp 1 20 325 2.75 Runtime 15 min Postrun 325° C./min for 3.5 min InletSplit/Splitless Temp 280° C. Mode Pulsed Splitless, Constant Flow Flow1.2 mL/min Pulse Press 25 psi Pulse Time 0.5 min Purge Time 0.5 minPurge Flow 50 mL/min Column DB-5MSUI part # (122-5512UI) 15 m × 0.25 mmid × 0.25 μm film Outlet Pressure Programmed for constant MSD restrictorflow (3.75 psig initial) Injection volume 1 μL MSD Agilent 5975C SolventDelay 2 min Acquisition Mode SIM SIM Ions 71, 85, 207 Dwell 10 msec TIDON Quad Temp 180° C. Source Temp 230° C. Transfer Line 300° C. TuneAtune, Gain 1 Backflush Device Post-column Purged Union withoverpressure vent MSD restrictor 1.0 m × 0.15 mm id inert fused silicatubing Restrictor Flow 1.8 mL/min Constant Flow Backflush 3.5 min, 325°C., 23.3 psig H₂ Addition Added to makeup H₂ Restrictor 3.0 m × 0.05 mmid fused silica tubing H₂ Pressure Programmed for constant flow of 5μL/min H₂ into MSD

FIG. 8 is a TIC that was typical of this Example when hydrogen wasadded.

A series of twenty-two replicate runs of the sample were made with nohydrogen added as a control. Because the column 246 was programmed up to325° C. and was a relatively new column, the source contamination fromcolumn bleed was expected to make the response of serial injectionsdrop. This degradation in performance was in fact observed as shown inthe response data provided in TABLE 2 below.

TABLE 2 Raw Integrator Areas for 22 Consecutive Runs of the Sample withNo Hydrogen Added run # n-C₁₄ area n-C₁₅ area n-C₁₆ area 1 65279406684730 67316710 2 6163040 6365260 6411940 3 6068450 6265900 6323490 45985550 6192020 6253440 5 5920670 6126290 6178460 6 5913440 61037206171680 7 5925520 6112470 6168160 8 5858280 6047730 6099580 9 58719506049400 6121840 10 5812020 5989770 6056490 11 5820170 6004660 6047150 125748320 5937110 6000790 13 5761850 5940150 6009640 14 5718320 58964305957680 15 5726420 5906800 5961500 16 5725410 5909500 5978280 17 57041205894010 5944330 18 5658460 5836330 5909420 19 5588440 5766990 5836070 205548320 5731290 5806550 21 5577990 5766070 5833330 22 5536550 57235605785420

FIG. 9 is a plot of the data from TABLE 2, normalized to the firstinjection and plotted for the three compounds. FIG. 9 shows that theresponse falls 15% for all three compounds.

The series of analyses was repeated, but this time with the hydrogenadded at 0.005 mL/min as described above. The response data is providedin TABLE 3 below. FIG. 10 is a plot of the data from TABLE 3, normalizedto the first injection and plotted for the three compounds. TABLE 3 andFIG. 10 demonstrate that the response now remained constant for allthree compounds, thus demonstrating that added hydrogen eliminated thedegradation in the response.

TABLE 3 Raw Integrator Areas for 21 Consecutive Runs of the Sample with5 μL/min Hydrogen Added run # n-C₁₄ area n-C₁₅ area n-C₁₆ area 1 56503205795110 5814900 2 5590770 5714370 5751740 3 5529930 5650690 5680710 45511490 5634980 5669660 5 5530050 5658120 5687170 6 5498250 56119805650740 7 5471190 5596170 5633590 8 5445580 5570350 5609500 9 54481405573710 5609970 10 5505020 5629310 5677190 11 5578850 5715670 5760110 125556950 5680140 5714160 13 5604790 5740080 5786420 14 5602550 57420705766270 15 5622990 5766140 5806920 16 5631060 5770860 5804230 17 56345905760410 5819640 18 5683250 5807250 5871830 19 5598700 5740670 5794060 205661630 5797440 5843810 21 5681120 5813190 5860870

Example 6 On-Line Conditioning

This Example described an analysis of a sample of semi-volatilepollutants. Some of these compounds are polar and exhibit activityproblems.

FIG. 11 is a schematic view of another example of an MS system 1100configured in particular for on-line conditioning and utilized in thisExample. The MS system 1100 includes many of the same components as theMS system 100 illustrated in FIG. 1, although for simplicity some ofthese components are not illustrated in FIG. 11. As compared with FIG. 1and FIG. 7, similar components are designated in FIG. 11 by the samereference numerals. The MS system 1100 illustrated in FIG. 11 includes afirst flow controller 308 for the conditioning gas and an associatedconditioning gas line 310, and a second flow controller 314 for anauxiliary gas and an associated auxiliary gas line 316. The flowcontrollers 308, 314 utilized in this Example were programmable EPCs.The conditioning gas line 310 is connected to the auxiliary gas line 316at a point outside the GC housing 234 by any suitable plumbing structuresuch as a union (not shown). In this Example, the analytes are at a verylow concentration of 200 pg/μL. Because there can be chromatographiclosses of some of the active compounds at low levels, the MS system 1100utilized a deactivated post-column flow splitter 1104 and an FID 272located outside the GC housing 234. Accordingly, the outlet of thecolumn 246 is connected to the purged splitter 1104. A first gas outletline 1108 interconnects the purged splitter 1104 and the ion source 120.The first gas outlet line 1108 may be considered as an extension of thecolumn 246 or alternatively as a separate gas transfer line. A secondgas outlet line 278 interconnects the purged splitter 1104 and the FID272. The flow splitter 1104 divides the column effluent equally betweenthe mass spectrometer 104 and the FID 272. The FID response is verystable and does not change with time. The FID 272 therefore makes anexcellent reference for tracking response changes in the massspectrometer 104, even for compounds with variable degrees of loss inthe inlet.

In this Example, the carrier gas was helium, the conditioning gas washydrogen, and the auxiliary gas was helium. The helium carrier gas wassupplied to the inlet of the column 246 at a pressure of about 25 psiand flowed through the column 246 at a constant rate of 0.95 mL/min. Thefirst flow controller 308 supplied hydrogen through a restrictor 334,after which the flow rate was 0.08 mL/min. The second flow controller314 supplied helium as a make-up gas to the flow splitter 1104 at aconstant pressure of 2 psig and at a flow rate of 3.05 mL/min. As aresult, the helium flowed to the mass spectrometer 104 and the FID 272each at 2 mL/min. Because the restrictors (not shown) from the flowsplitter 1104 to the mass spectrometer 104 and FID 272 are in the oven(the heated GC housing 234) and the flow splitter 1104 is maintained atconstant pressure by the second flow controller 314, the flow of heliumto each of the mass spectrometer 104 and FID 272 dropped from 2 mL/minat the initial oven temperature of 40° C. to 0.67 mL/min at 320° C. Theamount of hydrogen reaching the mass spectrometer 104, however, stayedconstant at 0.04 mL/min. Thus, by the configuration illustrated in FIG.11, samples can be easily run with or without implementing theconditioning process employed in this Example (i.e., turning thehydrogen flow on or off).

TABLE 4 below lists the instrument parameters for this Example.

TABLE 4 Instrument Parameters Ramp ° C./min ° C. Hold min Initial 40 2.5Ramp 1 25 320 2.8 Runtime 16.5 min Postrun n/a ° C./min for 0 min InletMultimode Temp 320° C. Mode Pulsed Splitless, Constant Flow Flow 0.95mL/min (adj to lock) Pulse Press 25 psi Pulse Time 1.4 min Purge Time1.4 min Purge Flow 50 mL/min Column DB-5MSUI part # (121-5523UI) 20 m ×0.18 mm id × 0.36 μm film Outlet Pressure Constant at 2 psig Injectionvolume 1 μL MSD Agilent 5975C Solvent Delay 3.2 min Acquisition Mode SIMSIM Ions 59 ions in 17 Groups Dwell 5 to 50 msec TID ON Quad Temp 180°C. Source Temp 350° C. Transfer Line 320° C. Tune Atune, Gain 1Backflush Device Post-column P3-way splitter with overpressure vent MSDRestrictor Inert fused silica tubing FID Restrictor 0.53 m × 0.18 mm idRestrictor Flows 2.0 mL/min at 40 C. H₂ Addition Added to makeup H₂ Flow2% of the total flow to each detector

FIG. 12 is an MS SIM TIC and an FID chromatogram obtained from thisExample with hydrogen added. The eight compounds of the sample arelisted. All compounds were present at 200 pg into the column 246 andthus at 100 pg to the mass spectrometer 104 and FID 272 each.

A series of twenty replicate runs of the sample were made with nohydrogen added as a control. The areas measured by the mass spectrometer104 were divided by the areas measured by the FID 272. The ratios werethen normalized to that of the first injection and plotted. To make theextent of any drop in responses clearer the normalized ratios from onlythe first five and last five injections are plotted. FIG. 13 is a plotof this data. Because the column 246 was programmed up to 320° C. andwas a relatively new column, the source contamination from column bleedwas expected to make the ratios of serial injections drop. Thisdegradation in performance was in fact observed as shown in FIG. 13. Inthe worst case, Trifluralin, the drop in the MS signal was 60%.

FIG. 14 shows the results of the same experiment, except this time withthe hydrogen added at 40 μL/min to each of the mass spectrometer 104 andFID 272. As seen in FIG. 14, the added hydrogen eliminates the drop inresponse.

Example 7 On-Line Conditioning

This Example describes an analysis of a sample of a mixture of solventsincluding water. This Example was particularly intended to determine theeffect of the presently disclosed conditioning process on the reduced MSresponse that results from the injection of samples containing largeamounts of water. For instance, this problem is observed when employingaqueous headspace injections.

FIG. 15 is a schematic view of another example of an MS system 1500configured in particular for on-line conditioning and utilized in thisExample. The MS system 1500 includes many of the same components as theMS system 100 illustrated in FIG. 1, although for simplicity some ofthese components are not illustrated in FIG. 15. As compared with FIGS.1, 7 and 11, similar components are designated in FIG. 15 by the samereference numerals. The MS system 1500 illustrated in FIG. 15 includes afirst flow controller 308 for the conditioning gas and an associatedconditioning gas line 310, and a second flow controller 314 for anauxiliary gas and an associated auxiliary gas line 316. The flowcontrollers 308, 314 utilized in this Example were programmable EPCs.The MS system 1500 further includes a purged flow splitter 1104 in theGC housing 234 and an FID 272 outside the GC housing 234. Accordingly,the outlet of the column 246 is connected to the purged splitter 1104. Afirst gas outlet line 1108 interconnects the purged splitter 1104 andthe ion source 120. The first gas outlet line 1108 may be considered asan extension of the column 246 or alternatively as a separate gastransfer line. The conditioning gas line 310 is connected to a conduitof the GC/MS interface 112 that coaxially surrounds the first gas outletline 1108, such that the conditioning gas flows through the annularspace defined between the first gas outlet line 1108 and the conduit.The conditioning gas line 310 is connected to a port of the conduitnormally utilized for introducing CI reagent gases into the ion source120. A second gas outlet line 278 interconnects the purged splitter 1104and the FID 272. The flow splitter 1104 divides the column effluentequally between the mass spectrometer 104 and the FID 272.

In this Example, the carrier gas was helium, the conditioning gas washydrogen, and the auxiliary gas was helium. The helium carrier gas wassupplied to the inlet of the column 246 at a pressure of about 14 psiand flowed through the column 246 at a constant rate of 1.0 mL/min. Thefirst flow controller 308 supplied hydrogen through a restrictor 334,after which the flow rate was 0.07 mL/min. The second flow controller314 supplied helium to the flow splitter 1104 at a constant pressure of3.8 psig and at a flow rate of 5 mL/min. As a result, the helium flowedto the mass spectrometer 104 and the FID 272 each at 3 mL/min (at aninitial oven temperature of 40° C.). Because the restrictors (not shown)from the flow splitter 1104 to the mass spectrometer 104 and FID 272 arein the oven (the heated GC housing 234) and the flow splitter 1104 ismaintained at constant pressure by the second flow controller 314, theflow of helium to each of the mass spectrometer 104 and FID 272 droppedfrom 3 mL/min at the initial oven temperature of 40° C. to 1.36 mL/minat 220° C. The amount of hydrogen reaching the mass spectrometer 104,however, stayed constant at 0.07 mL/min. Thus, by the configurationillustrated in FIG. 15, samples can be easily run with or withoutimplementing the conditioning process employed in this Example (i.e.,turning the hydrogen flow on or off). In this Example, the injectionsolvent for the mixture of solvents was water. The injection was a 20:1split injection of 1 μL of the mixture, putting 50 nL (50 μg) of waterinto the ion source 120 with each injection.

TABLE 5 below lists the instrument parameters for this Example.

TABLE 5 Instrument Parameters Ramp ° C./min ° C. Hold min Initial 40 1Ramp 1 10 220 2 Runtime 21 min Inlet Split/Splitless Temp 280° C. ModeSplit, Constant Flow Flow 1.0 mL/min Inlet Press 14 psi Split Flow 20mL/min Column DB-5MSUI part # (122-5536UI) 30 m × 0.25 mm id × 0.5 μmfilm Outlet Pressure Constant at 3.8 psig Injection volume 1 μL MSDAgilent 5975C Solvent Delay 0 min Acquisition Mode SIM SIM Ions 17 ionsin 3 Groups Dwell 25 msec TID OFF Quad Temp 180° C. Source Temp 300° C.Transfer Line 260° C. Tune Atune, Gain 1 Splitter Device Post-column2-way splitter Splitter Pressure Constant at 3.8 psig Restrictors Inertfused silica tubing MSD Restrictor 0.95 mm × 0.15 mm id FID Restrictor0.35 m × 0.15 mm id Restrictor Flows 3.0 mL/min at 40 C. H₂ AdditionAdded at source H₂ Flow 70 μL/min H₂ Restrictor 25 mm × 0.015 mm id

FIG. 16 is an MS SIM TIC and an FID chromatogram obtained from thisExample with hydrogen added. The nine solvent compounds of the sampleare listed. All compounds were present at 1 ng into the column 246 andthus at 500 pg to the mass spectrometer and FID each.

A series of nine replicate runs of the sample were made with hydrogenadded, followed by eleven replicate runs of the sample made with nohydrogen added as a control. The areas measured by the mass spectrometer104 were divided by the areas measured by the FID 272. The ratios werethen normalized to that of the first injection made with hydrogen addedand plotted. FIG. 17 is a plot of this data. As shown in FIG. 17, in theabsence of hydrogen the MS response signals were suppressed between 40%and 75% for all compounds except nitrobenzene. By comparison, thepresence of hydrogen significantly improved the MS performance. FIG. 17thus demonstrates the improvement in performance with samples with whichwater is injected.

Example 8 On-Line Conditioning

In this Example, the relative amounts of hydrogen and helium werereversed, and hydrogen was utilized as the carrier gas for running asample through the column. It has been observed that when setting up aGC/MS system with hydrogen as the carrier gas, as soon as the ion sourceis turned on, a very high background of many ions is observed. FIG. 18shows a typical spectrum of background ion masses observed whenemploying only hydrogen as the carrier gas in a typical GC/MS system.The high background is accompanied by a poor S/N ratio and poor peakshapes, as seen in the TIC for the analytes (FIG. 20). This backgroundtakes a very long time to come down. It often takes a few weeks ofoperation before the background drops to a level at which the peak shapeand S/N performance are acceptable.

In this Example, the addition of helium into the hydrogen gas stream ata point upstream of the ion source was found to facilitate cleaning theion source during use. The flow of helium was maintained for over 30chromatographic runs, and was found to greatly improve the background inone day instead of a few weeks. It is believed that the presence of thehelium in the ion source may increase the effectiveness of the hydrogenas a conditioning agent. Without wishing to be bound by any oneparticular theory, it is possible the partial pressure of helium in thepresence of hydrogen provides a higher overall pressure inside thesource which increases the opportunity for surface related phenomenarelated to the “cleaning” or surface conditioning. This is becausespecies such as metastable helium are also generated, which may assistin the conditioning activity, as well as the possibility of othercharge-exchange or dissociated species that may be absent in purehydrogen.

FIG. 19 is a schematic view of another example of an MS system 1900configured in particular for on-line conditioning and utilized in thisExample. The MS system 1900 includes many of the same components as theMS system 100 illustrated in FIG. 1, although for simplicity some ofthese components are not illustrated in FIG. 19. As compared with FIGS.1, 7, 11 and 15, similar components are designated in FIG. 19 by thesame reference numerals. The MS system 1900 illustrated in FIG. 19 aconditioning gas source that in this Example also serves as the carriergas source (not shown) communicating with the inlet of the column 246.That is, the hydrogen serves the dual roles of a carrier gas for thesample and a conditioning gas for the MS system 1900. The MS system 1900further includes a flow controller 314 for an auxiliary gas (helium inthis Example) and an associated auxiliary gas line 316. The flowcontroller 314 utilized in this Example was a programmable EPC. The MSsystem 1900 further includes a purged union 326 in the GC housing 234 towhich the outlet of the column 246 and the auxiliary gas line 316 areconnected. A gas transfer line 330 interconnects the purged union 326and the ion source 120. The gas transfer line 330 may be considered asan extension of the column 246 or alternatively as a separate gas line.The hydrogen carrier gas was supplied to the inlet of the column 246 ata pressure of about 14 psi and flowed through the column 246 at aconstant rate of 1.11 mL/min. The purged union facilitated 326 theaddition of the stream of helium to the sample/hydrogen stream flowingfrom the column 246. The flow controller 314 supplied helium at a flowrate of 0.13 mL/min. During the chromatographic run, the hydrogen/heliummixture flowed into the ion source 120 at 1.24 mL/min.

TABLE 6 below lists the instrument parameters for this Example.

TABLE 6 Instrument Parameters Ramp ° C./min ° C. Hold min Initial 90 0.0Ramp 1 20 325 2.5 Runtime 14.5 min Inlet Split/Splitless Temp 280° C.Mode Pulsed Splitless, Constant Pressure Pulse Pressure 40 psig H₂ until0.75 min Pressure 14.0 psig H₂ Purge Flow 50 mL/min Purge time 0.75 minSeptum Purge Switched, 3 mL/min Column DB-5MSUI part # (121-5522UI) 20 m× 0.18 mm id × 0.18 μm film Initial Flow 1.16 mL/min Outlet PressureVacuum Injection volume 1 μL MSD Agilent 5975C Solvent Delay 1.5 minAcquisition Mode Scan Scan Range 40 to 570 Threshold 0 Sampling 1 QuadTemp 150° C. Source Temp 300° C. Transfer Line 300° C. Tune GainNormalized 1X He Addition Added with purged union He Flow 130 mL/min HeRestrictor 0.5 m × 0.05 mm id

FIG. 20 shows two TICs obtained from this Example. The top trace wasacquired shortly after the chromatographic run was initiated. The bottomtrace was acquired after the MS system 1900 became clean after abouttwenty-four hours and with the helium flow turned on. The sample was atoxicology test mix of twenty-eight compounds, which are listed in FIG.20. The improvement in S/N ratio and peak shape as a result of theaddition of the helium to the hydrogen carrier gas is clearly evidentfrom FIG. 20. As noted above, this cleaning effect may occur in a fewdays instead of a few weeks.

Exemplary Embodiments

Exemplary embodiments provided in accordance with the presentlydisclosed subject matter include, but are not limited to, the following:

1. A mass spectrometer (MS) system, comprising:

a mass spectrometer comprising a sample interface and an ionizationchamber communicating with the sample interface;

a conditioning gas line configured for supplying a conditioning gas;

means for operating in an analytical mode, configured for establishing asample flow path through the sample interface and into the ionizationchamber; and

means for operating in a conditioning mode, configured for establishinga conditioning gas flow path through the conditioning gas line and intothe mass spectrometer.

2. The MS system of embodiment 1, comprising a gas chromatograph (GC)housing communicating with the sample interface, wherein the sample gasflow path runs from the GC housing into the sample interface.

3. The MS system of embodiment 2, wherein the conditioning gas linecommunicates with the sample interface from a location in the GChousing.

4. The MS system of embodiment 1, comprising a column, the columncomprising a column inlet and a column outlet, wherein the column inletcommunicates with the conditioning gas line, the column outletcommunicates with the ionization chamber via the sample interface, andthe conditioning gas flow path runs into the column inlet and throughthe column.

5. The MS system of embodiment 4, comprising a carrier gas sourcecommunicating with the column, wherein the means for operating in theconditioning mode is configured for regulating respective flows of thecarrier gas and the conditioning gas into the column inlet, and theproportion of the carrier gas relative to the conditioning gas flowinginto the column inlet ranges from 0% to less than 100%.

6. The MS system of embodiment 4, wherein the column extends through thesample interface, the sample interface comprises a conduit communicatingwith the ionization chamber, the conditioning gas line communicates withthe conduit, and the conditioning gas flow path runs through theconduit.

7. The MS system of embodiment 6, comprising an auxiliary gas lineconfigured for supplying a reagent gas for chemical ionization andcommunicating with the conduit, and a flow control device communicatingwith the auxiliary gas line, wherein:

the conditioning gas line communicates with the flow control device;

the means for operating in the analytical mode is configured foroperating the flow control device to establish a reagent gas flow paththrough the auxiliary gas line, through the conduit and into theionization chamber; and

the means for operating in the conditioning mode is configured foroperating the flow control device to establish the conditioning gas flowpath from the conditioning gas line, through the auxiliary gas line,through the conduit and into the ionization chamber.

8. The MS system of embodiment 4, wherein the conditioning gas linecommunicates directly with the mass spectrometer separately from thecolumn.

9. The MS system of embodiment 4, comprising a flow splittercommunicating with the column, a gas outlet line communicating with theflow splitter, a gas detector communicating with the gas outlet line, amass analyzer communicating with the ionization chamber, and an iondetector communicating with the mass analyzer, wherein the flow splitteris configured for splitting a sample/gas flow in the column into a firstoutput flow directed into the ionization chamber and a second outputflow directed via the gas outlet line into the gas detector, and themeans for operating in the conditioning mode is configured fordetermining whether the MS system should be operated in the conditioningmode based on comparing a chromatogram or other analytical data producedfrom the ion detector from an analysis of a sample with a chromatogramor other analytical data produced from the gas detector from the sameanalysis.

10. The MS system of embodiment 1, comprising a column, the columncomprising a column inlet and a column outlet, wherein the column outletcommunicates with the ionization chamber via the sample interface, theconditioning gas line communicates with a section of the column betweenthe column inlet and the column outlet, and the conditioning gas flowpath runs into the section and through the column.

11. The MS system of embodiment 1, comprising an auxiliary gas sourcecommunicating with the conditioning gas line for supplying an auxiliarygas different from the conditioning gas, wherein the means for operatingin the conditioning mode is configured for regulating respective flowsof the auxiliary gas and the conditioning gas.

12. The MS system of embodiment 1, wherein the means for operating inthe conditioning mode is configured for maintaining the ionizationchamber at a temperature ranging from −20 to 800° C.

13. The MS system of embodiment 12, wherein the means for operating inthe conditioning mode is configured for operating an ionization deviceto excite the conditioning gas in the ionization chamber.

14. The MS system of embodiment 1, wherein the means for operating inthe conditioning mode is configured for controlling a temperatureselected from the group consisting of: a temperature of a housingcommunicating with the sample interface; a temperature of a columncommunicating with the sample interface; a temperature of the sampleinterface; a temperature of the ionization chamber; a temperature of amass analyzer communicating with the ionization chamber; a temperatureof a detector of the mass spectrometer; and a combination of two of moreof the foregoing.

15. The MS system of embodiment 1, wherein the means for operating inthe conditioning mode comprises a device selected from the groupconsisting of a manual user input, an electronic processor, a logicinstruction executable by an electronic processor residing in a localmemory of the MS system or a remote memory accessible by the electronicprocessor, or a combination of two or more of the foregoing.

16. The MS system of embodiment 1, wherein the means for operating inthe conditioning mode is configured for evaluating a parameter of the MSsystem and, based on the parameter, determining whether the MS systemshould be operated in the conditioning mode.

17. The MS system of embodiment 16, wherein the parameter is selectedfrom the group consisting of: a number of times a component of the MSsystem has been operated in the analytical mode prior to evaluating theparameter; an amount of time elapsed prior to evaluating the parameter;a quality of a chromatogram, mass spectrum or other analytical dataproduced by the MS system under predetermined operating conditions; asignal-to-noise ratio of a chromatogram, mass spectrum or otheranalytical data produced by the MS system under predetermined operatingconditions; a measurement of an abundance of ions of one or moreselected mass-to-charge ratios taken while operating in the conditioningmode; the presence of stationary phase material separated from astationary phase support of the column; and a combination of two or moreof the foregoing.

18. The MS system of embodiment 16, wherein the means for operating inthe analytical mode is configured for taking an action based ondetermining whether the MS system should be operated in the conditioningmode, and the action is selected from the group consisting of switchingthe operation of the MS system to the conditioning mode, scheduling atime for switching the operation of the MS system to the conditioningmode, modifying a pre-scheduled time for switching the operation of theMS system to the conditioning mode, producing a user-readable indicationthat the MS system should be operated in the conditioning mode, and acombination of two of more of the foregoing.

19. The MS system of embodiment 1, comprising a mass analyzercommunicating with the ionization chamber and an ion detectorcommunicating with the mass analyzer, wherein the means for operating inthe conditioning mode comprises means for monitoring a chromatogram,mass spectrum or other analytical data produced from the ion detectorwhile operating in the conditioning mode.

20. A method for operating a mass spectrometer (MS) system, the methodcomprising:

operating the MS system in an analytical mode by introducing a sampleand a carrier gas into an ionization chamber of the MS system;

ceasing operating the MS system in the analytical mode by ceasing theflowing of the sample; and

operating the MS system in a conditioning mode to condition one or morecomponents of a mass spectrometer of the MS system by flowing aconditioning gas into the mass spectrometer, wherein the conditioninggas is different from the carrier gas.

21. The method of embodiment 20, wherein the carrier gas is selectedfrom the group consisting of helium, nitrogen, and argon.

22. The method of embodiment 20 or 21, wherein the conditioning gas isflowed from a source containing a blend of the conditioning gas and anauxiliary gas different from the conditioning gas.

23. The method of embodiment 22, wherein the proportion of theconditioning gas relative to the auxiliary gas in the source ranges from0% to less than 100% by volume.

24. The method of embodiment 22, wherein the auxiliary gas is the sameas the carrier gas.

25. The method of any one of embodiments 20-24, wherein ceasingoperating in the analytical mode comprises ceasing the flowing of thecarrier gas.

26. The method of any one of embodiments 20-24, wherein ceasingoperating in the analytical mode comprises reducing a flow rate of thecarrier gas, and operating in the conditioning mode comprises continuingto flow the carrier gas at the reduced flow rate.

27. The method of any one of embodiments 20-26, wherein flowing theconditioning gas into the mass spectrometer comprises a step selectedfrom the group consisting of: flowing the conditioning gas with thecarrier gas into a column inlet of a column communicating with theionization chamber; flowing the conditioning gas into a section of thecolumn between the column inlet and a column outlet of the column;flowing the conditioning gas into a conduit of a sample interface of theMS system through which the column extends, wherein conduit and thecolumn communicate separately with the ionization chamber; flowing theconditioning gas directly into the mass spectrometer via a gas lineseparate from the column; and a combination of two or more of theforegoing.

28. The method of any one of embodiments 20-27, wherein the conditioninggas is flowed through a column and into the ionization chamber, andcomprising regulating respective flows of the carrier gas and theconditioning gas such that the proportion of the carrier gas flowinginto the column inlet ranges from 0% to less than 100%.

29. The method of any one of embodiments 20-27, wherein a columncommunicates with the ionization chamber, and the conditioning gas isflowed into a section of the column between a column inlet and a columnoutlet of the column, through the column and into the ionizationchamber, and comprising regulating the flow of the conditioning gas andan auxiliary gas into the section.

30. The method of embodiment 29, wherein the auxiliary gas is the sameas the carrier gas.

31. The method of any one of embodiments 20-27, wherein the MS systemcomprises a sample interface through which the column extends, and theinterface comprises a conduit communicating with the ionization chamber,and wherein operating in the conditioning mode comprises flowing theconditioning gas through the conduit and into the ionization chamber,operating in the analytical mode comprises flowing a reagent gas throughthe conduit and into the ionization chamber to perform chemicalionization, and ceasing operating in the analytical mode comprisesceasing the flowing of the reagent gas into the conduit, wherein thereagent gas is different from the conditioning gas.

32. The method of any one of embodiments 20-31, wherein operating in theconditioning mode comprises maintaining the ionization chamber at atemperature ranging from −20 to 800° C.

33. The method of embodiment 32, wherein operating in the conditioningmode comprises exciting the conditioning gas in the ionization chamber.

34. The method of any one of embodiments 20-33, wherein operating in theconditioning mode comprises controlling a temperature selected from thegroup consisting of: a temperature of a housing in which a column isdisposed, wherein the column communicates with the ionization chamber; atemperature of the column; a temperature of a sample interface throughwhich the column extends; a temperature of the ionization chamber; atemperature of the mass analyzer; a temperature of a detector of themass spectrometer; and a combination of two of more of the foregoing.

35. The method of any one of embodiments 20-34, comprising evaluating aparameter of the MS system and, based on the parameter, determiningwhether the MS system should be operated in the conditioning mode.

36. The method of embodiment 35, wherein the parameter is selected fromthe group consisting of: a number of times a component of the MS systemhas been operated in the analytical mode prior to evaluating theparameter; an amount of time elapsed prior to evaluating the parameter;a quality of a chromatogram, mass spectrum or other analytical dataproduced by the MS system under predetermined operating conditions; asignal-to-noise ratio of a chromatogram, mass spectrum or otheranalytical data produced by the MS system under predetermined operatingconditions; a measurement of an abundance of ions of one or moreselected mass-to-charge ratios taken while operating in the conditioningmode; the presence of stationary phase material separated from astationary phase support of the column; and a combination of two or moreof the foregoing.

37. The method of embodiment 36, wherein if it is determined that the MSsystem should be operated in the conditioning mode, performing a stepselected from the group consisting of switching the operation of the MSsystem from the analytical mode to the conditioning mode, scheduling atime for switching the operation of the MS system to the conditioningmode, modifying a pre-scheduled time for switching the operation of theMS system to the conditioning mode, producing a user-readable indicationthat the MS system should be operated in the conditioning mode, and acombination of two of more of the foregoing.

38. The method of any one of embodiments 20-37, comprising flowing thesample and the carrier gas flow through a stationary phase of the columnto produce a mixture of the carrier gas and separated components of thesample, splitting the mixture into a first output flow directed into theionization chamber and a second flow directed to a gas detector separatefrom an ion detector associated with the ionization chamber, producingrespective chromatograms or other analytical data from the ion detectorand the gas detector, and determining whether the MS system should beoperated in the conditioning mode based on comparing the respectivechromatograms or other analytical data.

39. The method of any one of embodiments 20-38, comprising monitoring achromatogram, mass spectrum or other analytical data produced by the MSsystem while operating in the conditioning mode.

40. A mass spectrometer (MS) system, comprising:

a mass spectrometer comprising a sample interface and an ionizationchamber communicating with the sample interface;

a conditioning gas line configured for communicating with a conditioninggas source and for directing a conditioning gas toward the massspectrometer; and

means for regulating respective flows of a carrier gas and theconditioning gas into the mass spectrometer.

41. The MS system of embodiment 40, wherein the means for regulatingrespective flows is configured for regulating such that the proportionof the conditioning gas flowing into the mass spectrometer ranges from0% to less than 100% by volume.

42. The MS system of embodiment 40, comprising a gas chromatograph (GC)housing communicating with the sample interface, wherein theconditioning gas line communicates with the sample interface from alocation in the GC housing

43. The MS system of embodiment 40, comprising a column, the columncomprising a column inlet and a column outlet, wherein the column inletcommunicates with the conditioning gas line, and the column outletcommunicates with the ionization chamber via the sample interface.

44. The MS system of embodiment 43, wherein the column extends throughthe sample interface, the sample interface comprises a conduitcommunicating with the ionization chamber, and the conditioning gas linecommunicates with the conduit.

45. The MS system of embodiment 44, comprising an auxiliary gas linecommunicating with the conduit for supplying a reagent gas for chemicalionization, and a flow control device communicating with the auxiliarygas line, wherein the conditioning gas line communicates with the flowcontrol device, and the means for regulating respective flows isconfigured for operating the flow control device to control respectiveflows of the conditioning gas and the reagent gas through the auxiliarygas line.

46. The MS system of embodiment 43, wherein the conditioning gas linecommunicates directly with the mass spectrometer separately from thecolumn.

47. The MS system of embodiment 43, comprising a flow splittercommunicating with the column, a gas outlet line communicating with theflow splitter, a gas detector communicating with the gas outlet line, amass analyzer communicating with the ionization chamber, and an iondetector communicating with the mass analyzer, wherein the flow splitteris configured for splitting a sample/gas flow in the column into a firstoutput flow directed into the ionization chamber and a second outputflow directed via the gas outlet line into the gas detector, and themeans for regulating respective flows is configured for regulating basedon comparing a chromatogram or other analytical data produced from theion detector from an analysis of a sample with a chromatogram or otheranalytical data produced from the gas detector from the same analysis.

48. The MS system of embodiment 40, comprising a column, the columncomprising a column inlet and a column outlet, wherein the column outletcommunicates with the ionization chamber via the sample interface, andthe conditioning gas line communicates with a section of the columnbetween the column inlet and the column outlet.

49. The MS system of embodiment 48, comprising an auxiliary gas sourcecommunicating with the conditioning gas line for supplying an auxiliarygas different from the conditioning gas, wherein the means forregulating respective flows is configured for regulating respectiveflows of the auxiliary gas and the conditioning gas, and the proportionof the auxiliary gas flowing through the conditioning gas line rangesfrom 0% to less than 100%.

50. The MS system of embodiment 40, wherein the means for regulatingrespective flows is configured for evaluating a parameter of the MSsystem, and regulating the flow of the conditioning gas based on theparameter.

51. The MS system of embodiment 50, wherein the parameter is selectedfrom the group consisting of: a number of times a component of the MSsystem has been operated to perform sample analyses prior to evaluatingthe parameter; an amount of time elapsed prior to evaluating theparameter; a quality of a chromatogram, mass spectrum or otheranalytical data produced by the MS system under predetermined operatingconditions; a signal-to-noise ratio of a chromatogram, mass spectrum orother analytical data produced by the MS system under predeterminedoperating conditions; a measurement of an abundance of ions of one ormore selected mass-to-charge ratios taken while operating the MS systemto analyze a sample; the presence of stationary phase material separatedfrom a stationary phase support of the column; the composition of asample matrix to be flowed through the column; the composition of astationary phase supported in the column; an inside diameter of thecolumn; the reactivity of one or more components of the sample matrixwith the conditioning gas; and a combination of two or more of theforegoing.

52. The MS system of embodiment 40, comprising a heating deviceconfigured for varying a temperature of a column or a temperature in ahousing according to a temperature profile, wherein the housingcommunicates with the sample interface, and the means for regulatingrespective flows is configured for maintaining the flow of theconditioning gas at a constant flow rate while the temperature isvaried.

53. The MS system of embodiment 40, comprising an ionization deviceoperative in the ionization chamber, a mass analyzer communicating withthe ionization chamber, and an ion detector communicating with the massanalyzer, wherein the means for regulating respective flows isconfigured for regulating based on a desired ratio of the abundance ofconditioning gas ions to the abundance of carrier gas ions as measuredby operating the ionization device, the mass analyzer, and the iondetector.

54. The MS system of embodiment 53, wherein the means for regulatingrespective flows is configured for comparing a measured ratio of theabundance of conditioning gas ions to the abundance of carrier gas ionswith the desired ratio to determine whether a ratio difference betweenmeasured ratio and the desired ratio falls outside a desired range, andadjusting the flow of the conditioning gas relative to the carrier gasinto the ionization chamber to maintain the ratio difference within thedesired range.

55. A method for operating a mass spectrometer (MS) system, the methodcomprising:

introducing a sample and a carrier gas into an ionization chamber of theMS system;

while introducing the sample and the carrier gas, flowing a conditioninggas into a mass spectrometer of the MS system, wherein the conditioninggas is different from the carrier gas; and

ionizing components of the sample in the ionization chamber, wherein theconditioning gas in the mass spectrometer does not substantially changethe mass spectral characteristics of analytes of the sample.

56. The method of embodiment 55, wherein the carrier gas is selectedfrom the group consisting of helium, nitrogen, and argon.

57. The method of embodiment 55 or 56, wherein the conditioning gas isflowed from a source containing a blend of the conditioning gas and anauxiliary gas different from the conditioning gas.

58. The method of embodiment 57, wherein the proportion of the auxiliarygas in the source ranges from 0% to less than 100% by volume.

59. The method of embodiment 57, wherein the auxiliary gas is the sameas the carrier gas.

60. The method of any one of embodiments 55-59, comprising mixing theflow of the carrier gas with the flow of the conditioning gas at a pointupstream of the ionization chamber, wherein mixing comprises a stepselected from the group consisting of: flowing the conditioning gas withthe carrier gas into a column inlet of a column; flowing theconditioning gas into a section of the column between the column inletand a column outlet of the column; and a combination of both of theforegoing.

61. The method of any one of embodiments 55-59, comprising mixing theflow of the carrier gas with the flow of the conditioning gas at themass spectrometer, wherein mixing comprises a step selected from thegroup consisting of: flowing the conditioning gas into a conduit of asample interface of the MS system through which a column extends,wherein the conduit and the column communicate separately with theionization chamber; flowing the conditioning gas directly into the massspectrometer via a gas line separate from the column; and a combinationof both of the foregoing.

62. The method of any one of embodiments 55-59, wherein the conditioninggas and the carrier gas are flowed through a column and into theionization chamber, and comprising regulating respective flows of thecarrier gas and the conditioning gas into the column inlet such that theproportion of the carrier gas relative to the conditioning gas flowingthrough the column ranges from 0% to less than 100%.

63. The method of any one of embodiments 55-59, wherein the conditioninggas is flowed into a section of a column between a column inlet and acolumn outlet of the column, through the column and into the ionizationchamber, and comprising flowing an auxiliary gas with the conditioninggas into the section, and regulating the flow of the auxiliary gasrelative to the flow of the conditioning gas such that the proportion ofthe auxiliary gas flowing into the section ranges from 0% to less than100%.

64. The method of embodiment 63, wherein the auxiliary gas is the sameas the carrier gas.

65. The method of any one of embodiments 55-59, wherein the MS systemcomprises a sample interface through which a column extends, and thesample interface comprises a conduit communicating with the ionizationchamber, and wherein the conditioning gas is flowed through the conduitand into the ionization chamber, and comprising flowing a reagent gasthrough the conduit and into the ionization chamber to perform chemicalionization, wherein the reagent gas is different from the conditioninggas.

66. The method of any one of embodiments 55-65, comprising regulatingthe flows of the carrier gas and the conditioning gas such that theproportion of the carrier gas flowing into the ionization chamber rangesfrom 0% to less than 100% by volume.

67. The method of any one of embodiments 55-66, comprising evaluating aparameter of the MS system, and regulating the flow of the conditioninggas based on the parameter.

68. The method of embodiment 67, wherein the parameter is selected fromthe group consisting of: a number of times a component of the MS housinghas been operated to perform sample analyses prior to evaluating theparameter; an amount of time elapsed prior to evaluating the parameter;a quality of a chromatogram, mass spectrum or other analytical dataproduced by the MS system under predetermined operating conditions; asignal-to-noise ratio of a chromatogram, mass spectrum or otheranalytical data produced by the MS system under predetermined operatingconditions; a measurement of an abundance of ions of one or moreselected mass-to-charge ratios taken while operating the MS system toanalyze a sample; the presence of stationary phase material separatedfrom a stationary phase support of the column; the composition of asample matrix to be flowed through the column; the composition of astationary phase supported in the column; an inside diameter of thecolumn; the reactivity of one or more components of the sample matrixwith the conditioning gas; and a combination of two or more of theforegoing.

69. The method of any one of embodiments 55-68, comprising varying atemperature of a column or a temperature in a housing in which thecolumn is disposed according to a temperature profile, and maintainingthe flow of the conditioning gas at a constant flow rate while varyingthe temperature.

70. The method of any one of embodiments 55-69, wherein the MS systemcomprises an ionization device operative in the ionization chamber, amass analyzer communicating with the ionization chamber, and an iondetector communicating with the mass analyzer, and comprising regulatingthe flow of the conditioning gas relative to the carrier gas into theionization chamber based on a desired ratio of the abundance ofconditioning gas ions to the abundance of carrier gas ions as measuredby operating the ionization device, the mass analyzer, and the iondetector.

71. The method of embodiment 70, comprising comparing a measured ratioof the abundance of conditioning gas ions to the abundance of carriergas ions with the desired ratio to determine whether a ratio differencebetween measured ratio and the desired ratio falls outside a desiredrange, and adjusting the flow of the conditioning gas relative to thecarrier gas into the ionization chamber to maintain the ratio differencewithin the desired range.

72. The method of any one of embodiments 55-71, comprising flowing thesample and the carrier gas flow through a stationary phase of a columnto produce a mixture of the carrier gas and separated components of thesample, splitting the mixture into a first output flow directed into theion source and a second flow directed to a gas detector separate from anion detector associated with the ion source, producing respectivechromatograms or other analytical data from the ion detector and the gasdetector, and regulating the flow of the conditioning gas relative tothe carrier gas into the ionization chamber based on comparing therespective chromatograms or other analytical data.

73. A mass spectrometer (MS) system, comprising:

a mass spectrometer comprising a sample interface and an ionizationchamber communicating with the sample interface;

a carrier gas line communicating with the sample interface andconfigured for supplying a carrier gas selected from the groupconsisting of hydrogen, argon, ammonia, and methane;

an auxiliary gas line configured for adding an auxiliary gas to thecarrier gas, wherein the auxiliary gas is different from the carriergas; and

means for regulating respective flows of the carrier gas and theauxiliary gas into the ionization chamber.

74. The MS system of embodiment 73, wherein the auxiliary gas isselected from the group consisting of helium, nitrogen, and argon.

75. The MS system of embodiment 73, wherein the carrier gas line isconfigured for supplying the carrier gas blended with another gasdifferent from the carrier gas.

76. The MS system of embodiment 75, wherein the proportion of the othergas in the blend ranges from 0% to less than 100% by volume.

77. The MS system of embodiment 75, wherein the other gas that isblended with the carrier gas is the same as the auxiliary gas.

78. A method for operating a mass spectrometer (MS) system, the methodcomprising:

flowing a sample and a carrier gas into an ionization chamber of the MSsystem, the carrier gas selected from the group consisting of hydrogen,argon, ammonia, and methane;

while flowing the sample and the carrier gas, flowing an auxiliary gasinto the ionization chamber, wherein the auxiliary gas is different fromthe carrier gas; and

ionizing components of the sample in the ionization chamber.

79. The method of embodiment 78, wherein the auxiliary gas is selectedfrom the group consisting of helium, nitrogen, and argon.

80. The method of embodiment 78, wherein the carrier gas is flowed froma source containing a blend of the carrier gas and another gas differentfrom the carrier gas.

81. The method of embodiment 80, wherein the proportion of the other gasin the blend therewith ranges from 0% to less than 100% by volume.

82. The method of embodiment 80, wherein the other gas that is blendedwith the carrier gas is the same as the auxiliary gas.

83. A method for operating a mass spectrometer (MS) system, the methodcomprising:

flowing a sample and a hydrogen through a column and into an ionizationchamber of the MS system;

while flowing the sample and the hydrogen, flowing an auxiliary gas intoa mass spectrometer of the MS system, wherein the auxiliary gas isselected from the group consisting of helium, nitrogen, and argon; and

ionizing components of the sample in the ionization chamber.

84. The method of embodiment 83, wherein the auxiliary gas is helium.

85. The method of embodiment 83, wherein the hydrogen is flowed with theauxiliary gas from a source containing a blend of the hydrogen and theauxiliary gas.

86. The method of embodiment 83, wherein flowing the auxiliary gas intothe mass spectrometer comprises a step selected from the groupconsisting of: flowing the auxiliary gas with the hydrogen into a columninlet of the column; flowing the auxiliary gas into a section of thecolumn between the column inlet and a column outlet of the column;flowing the auxiliary gas into a conduit of a sample interface of the MSsystem, wherein the conduit and the column communicate separately withthe ionization chamber; flowing the auxiliary gas directly into the massspectrometer via a gas line separate from the column; and a combinationof two or more of the foregoing.

87. The method of embodiment 83, comprising regulating a flow of theauxiliary gas in the mass spectrometer relative to a flow of thehydrogen into the ionization chamber such that the proportion of theauxiliary gas flow ranges from 0% to less than 100%.

88. The method of embodiment 83, comprising operating the massspectrometer to measure a ratio of the abundance of carrier gas ions tothe abundance of auxiliary gas ions, and regulating the flow of theauxiliary gas into the mass spectrometer based on the measured ratio.

89. A mass spectrometer (MS) system, configured for performing themethod of embodiment 83.

90. A method for operating a mass spectrometer (MS) system, the methodcomprising flowing a conditioning gas into a mass spectrometer of the MSsystem without flowing a sample into the mass spectrometer.

91. The method of embodiment 90, comprising ionizing one or moremolecules in the mass spectrometer while flowing the conditioning gas.

92. The method of any one of the preceding claims, wherein theconditioning gas is flowed directly into the ionization chamber.

93. A method for operating a mass spectrometer (MS) system, the methodcomprising introducing a sample and a carrier gas into the MS system,wherein the carrier gas is a blend of helium and hydrogen.

94. The MS system or method of any one of the preceding claims, whereinthe MS system does not comprise a plasma ion source.

95. The MS system or method of any one of the preceding claims, whereinthe MS system comprises an ion mobility spectrometer (IMS), and theconditioning gas is not introduced into the IMS.

96. The MS system or method of any one of claims 1-94, wherein the MSsystem does not comprise an IMS.

97. A computer-readable storage medium comprising instructions forperforming the method of any one of the preceding claims.

98. An MS system comprising the computer-readable storage medium ofembodiment 97.

From the foregoing, it can be seen the embodiments described herein mayeliminate—or significantly lower the frequency of—conventional MSservicing tasks, such as removal, ex-situ cleaning, and re-installationof contaminated parts, and restore or improve the performance of an MSsystem. Application of an off-line, on-line, or both off-line andon-line conditioning process as described herein may rapidly improve thebackground of the MS system, including with respect to chemicallyadsorbed species such as water which otherwise would have a very slowrate of elimination, and species such as the solvents or hydrocarbonsadsorbed on MS components upon exposure to air during conventionalcleaning

It will be understood that one or more of the processes, sub-processes,and process steps described herein may be performed by hardware,firmware, software, or a combination of two or more of the foregoing, onone or more electronic or digitally-controlled devices. The software mayreside in a software memory (not shown) in a suitable electronicprocessing component or system such as, for example, the systemcontroller 168 schematically depicted in FIG. 1. The software memory mayinclude an ordered listing of executable instructions for implementinglogical functions (that is, “logic” that may be implemented in digitalform such as digital circuitry or source code, or in analog form such asan analog source such as an analog electrical, sound, or video signal).The instructions may be executed within a processing module, whichincludes, for example, one or more microprocessors, general purposeprocessors, combinations of processors, digital signal processors(DSPs), or application specific integrated circuits (ASICs). Further,the schematic diagrams describe a logical division of functions havingphysical (hardware and/or software) implementations that are not limitedby architecture or the physical layout of the functions. The examples ofsystems described herein may be implemented in a variety ofconfigurations and operate as hardware/software components in a singlehardware/software unit, or in separate hardware/software units.

The executable instructions may be implemented as a computer programproduct having instructions stored therein which, when executed by aprocessing module of an electronic system (e.g., the system controller168 in FIG. 1), direct the electronic system to carry out theinstructions. The computer program product may be selectively embodiedin any non-transitory computer-readable storage medium for use by or inconnection with an instruction execution system, apparatus, or device,such as a electronic computer-based system, processor-containing system,or other system that may selectively fetch the instructions from theinstruction execution system, apparatus, or device and execute theinstructions. In the context of this disclosure, a computer-readablestorage medium is any non-transitory means that may store the programfor use by or in connection with the instruction execution system,apparatus, or device. The non-transitory computer-readable storagemedium may selectively be, for example, an electronic, magnetic,optical, electromagnetic, infrared, or semiconductor system, apparatus,or device. A non-exhaustive list of more specific examples ofnon-transitory computer readable media include: an electrical connectionhaving one or more wires (electronic); a portable computer diskette(magnetic); a random access memory (electronic); a read-only memory(electronic); an erasable programmable read only memory such as, forexample, flash memory (electronic); a compact disc memory such as, forexample, CD-ROM, CD-R, CD-RW (optical); and digital versatile discmemory, i.e., DVD (optical). Note that the non-transitorycomputer-readable storage medium may even be paper or another suitablemedium upon which the program is printed, as the program can beelectronically captured via, for instance, optical scanning of the paperor other medium, then compiled, interpreted, or otherwise processed in asuitable manner if necessary, and then stored in a computer memory ormachine memory.

It will also be understood that the term “in signal communication” asused herein means that two or more systems, devices, components,modules, or sub-modules are capable of communicating with each other viasignals that travel over some type of signal path. The signals may becommunication, power, data, or energy signals, which may communicateinformation, power, or energy from a first system, device, component,module, or sub-module to a second system, device, component, module, orsub-module along a signal path between the first and second system,device, component, module, or sub-module. The signal paths may includephysical, electrical, magnetic, electromagnetic, electrochemical,optical, wired, or wireless connections. The signal paths may alsoinclude additional systems, devices, components, modules, or sub-modulesbetween the first and second system, device, component, module, orsub-module.

More generally, terms such as “communicate” and “in . . . communicationwith” (for example, a first component “communicates with” or “is incommunication with” a second component) are used herein to indicate astructural, functional, mechanical, electrical, signal, optical,magnetic, electromagnetic, ionic or fluidic relationship between two ormore components or elements. As such, the fact that one component issaid to communicate with a second component is not intended to excludethe possibility that additional components may be present between,and/or operatively associated or engaged with, the first and secondcomponents.

It will be understood that various aspects or details of the inventionmay be changed without departing from the scope of the invention.Furthermore, the foregoing description is for the purpose ofillustration only, and not for the purpose of limitation—the inventionbeing defined by the claims.

1.-20. (canceled)
 21. A method for operating a mass spectrometer (MS)system, the method comprising: introducing a sample and a carrier gasinto an ionization chamber of the MS system; and flowing a conditioninggas into the MS system, the conditioning gas comprising hydrogen gas,wherein the conditioning gas in the MS system does not substantiallychange the mass spectral characteristics of analytes of the sample, andthe carrier gas does not comprise hydrogen gas.
 22. The method of claim21, wherein the MS system comprises a collision cell.
 23. The method ofclaim 22, wherein the conditioning gas is flowed directly into thecollision cell.
 24. The method of claim 22, wherein the conditioning gasis flowed into the MS system upstream from the collision cell.
 25. Themethod of claim 22, wherein the conditioning gas is flowed into the MSsystem downstream from the collision cell.
 26. The method of claim 21,wherein the conditioning gas is flowed directly into an ion detector ofthe MS system.
 27. The method of claim 21, wherein the carrier gascomprises helium.
 28. The method of claim 21, wherein the carrier gas ishelium and the conditioning gas is hydrogen.
 29. The method of claim 21,wherein the conditioning gas is flowed into two or more locations in theMS system.
 30. The method of claim 29, wherein said two or morelocations include a collision cell.
 31. A method for operating an MSsystem, the method comprising: flowing a conditioning gas into a massspectrometer of the MS system without introducing a sample into the massspectrometer, wherein the mass spectrometer is conditioned by theconditioning gas; and introducing a sample with a carrier gas into theconditioned mass spectrometer and collecting analytical data from thesample, wherein the carrier gas does not comprise hydrogen gas, and theconditioning gas comprises hydrogen gas or ammonia.
 32. The method ofclaim 31, wherein the carrier gas comprises helium.
 33. The method ofclaim 31, wherein the conditioning gas comprises hydrogen.
 34. Themethod of claim 31, wherein the carrier gas is helium and theconditioning gas is hydrogen.
 35. The method of claim 31, wherein the MSsystem comprises a collision cell.
 36. The method of claim 35, whereinthe conditioning gas is flowed directly into the collision cell.
 37. Themethod of claim 31, wherein the conditioning gas is flowed directly intoan ion detector of the MS system.
 38. The method of claim 31, whereinthe conditioning gas is flowed into two or more locations in the MSsystem.
 39. The method of claim 38, wherein said two or more locationsinclude a collision cell.
 40. The method of claim 38, wherein said twoor more locations include an ion detector.